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Akira Kudo - One of the best experts on this subject based on the ideXlab platform.
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Periostin is required for the maintenance of muscle fibers during muscle regeneration
International Journal of Molecular Sciences, 2021Co-Authors: Naoki Ito, Yuko Miyagoesuzuki, Shinichi Takeda, Akira KudoAbstract:Skeletal muscle regeneration is a well-organized process that requires remodeling of the extracellular matrix (ECM). In this study, we revealed the protective role of Periostin, a matricellular protein that binds to several ECM proteins during muscle regeneration. In intact muscle, Periostin was localized at the neuromuscular junction, muscle spindle, and myotendinous junction, which are connection sites between muscle fibers and nerves or tendons. During muscle regeneration, Periostin exhibited robustly increased expression and localization at the interstitial space. Periostin-null mice showed decreased muscle weight due to the loss of muscle fibers during repeated muscle regeneration. Cultured muscle progenitor cells from Periostin-null mice showed no deficiencies in their proliferation, differentiation, and the expression of Pax7, MyoD, and myogenin, suggesting that the loss of muscle fibers in Periostin-null mice was not due to the impaired function of muscle stem/progenitor cells. Periostin-null mice displayed a decreased number of CD31-positive blood vessels during muscle regeneration, suggesting that the decreased nutritional supply from blood vessels was the cause of muscle fiber loss in Periostin-null mice. These results highlight the novel role of Periostin in maintaining muscle mass during muscle regeneration.
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Periostin in fibrillogenesis for tissue regeneration: Periostin actions inside and outside the cell
Cellular and Molecular Life Sciences, 2011Co-Authors: Akira KudoAbstract:More than 10 years have passed since the naming of Periostin derived from its expression sites in the periosteum and periodontal ligament. Following this finding, we have accumulated more data on the expression patterns of Periostin, and, finally, with the generation of Periostin-deficient mice, have revealed functions of Periostin in the regeneration of tissues in bone, tooth, heart, and skin, and its action in cancer invasion. Since Periostin is a matricellular protein, the first investigation of Periostin function showed its enhancement of cell migration by acting outside the cell. On the other hand, recent observations have demonstrated that Periostin functions in fibrillogenesis in association with extracellular matrix molecules inside the cell.
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delayed re epithelialization in Periostin deficient mice during cutaneous wound healing
PLOS ONE, 2011Co-Authors: Takashi Nishiyama, Isao Kii, Takeshi Kashima, Yoshinao Kikuchi, Atsushi Ohazama, Masashi Shimazaki, Masashi Fukayama, Akira KudoAbstract:Background Matricellular proteins, including Periostin, are important for tissue regeneration. Methods and Findings Presently we investigated the function of Periostin in cutaneous wound healing by using Periostin-deficient (−/−) mice. Periostin mRNA was expressed in both the epidermis and hair follicles, and Periostin protein was located at the basement membrane in the hair follicles together with fibronectin and laminin γ2. Periostin was associated with laminin γ2, and this association enhanced the proteolytic cleavage of the laminin γ2 long form to produce its short form. To address the role of Periostin in wound healing, we employed a wound healing model using WT and Periostin−/− mice and the scratch wound assay in vitro. We found that the wound closure was delayed in the Periostin−/− mice coupled with a delay in re-epithelialization and with reduced proliferation of keratinocytes. Furthermore, keratinocyte proliferation was enhanced in Periostin-overexpressing HaCaT cells along with up-regulation of phosphorylated NF-κB. Conclusion These results indicate that Periostin was essential for keratinocyte proliferation for re-epithelialization during cutaneous wound healing.
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Periostin is an extracellular matrix protein required for eruption of incisors in mice
Biochemical and Biophysical Research Communications, 2006Co-Authors: Isao Kii, Norio Amizuka, L I Minqi, Satoshi Kitajima, Yumiko Saga, Akira KudoAbstract:Abstract A characteristic tooth of rodents, the incisor continuously grows throughout life by the constant formation of dentin and enamel. Continuous eruption of the incisor is accompanied with formation of shear zone, in which the periodontal ligament is remodeled. Although the shear zone plays a role in the remodeling, its molecular biological aspect is barely understood. Here, we show that Periostin is essential for formation of the shear zone. Periostin−/− mice showed an eruption disturbance of incisors. Histological observation revealed that deletion of Periostin led to disappearance of the shear zone. Electron microscopy revealed that the disappearance of the shear zone resulted from a failure in digestion of collagen fibers in the Periostin−/− mice. Furthermore, immunohistochemical analysis using anti-Periostin antibodies demonstrated the restricted localization of Periostin protein in the shear zone. Periostin is an extracellular matrix protein, and immunoelectron microscopy showed a close association of Periostin with collagen fibrils in vivo. These results suggest that Periostin functions in the remodeling of collagen matrix in the shear zone.
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Immunohistochemical localization of Periostin in tooth and its surrounding tissues in mouse mandibles during development
The anatomical record. Part A Discoveries in molecular cellular and evolutionary biology, 2004Co-Authors: Hironobu Suzuki, Isao Kii, Norio Amizuka, Akira Kudo, Yoshiro Kawano, Kayoko Nozawa-inoue, Akiko Suzuki, Hiromasa Yoshie, Takeyasu MaedaAbstract:Previous reports have shown expression of immunoreactivity for Periostin, originally identified as osteoblast-specific factor-2, in the periosteum and periodontal ligament. However, the developmental changes in its expression and the detailed immunolocalization have remained veiled. The present study was undertaken to examine the spatiotemporal expression of this protein in teeth and their associated tissues of mice during development at light and electron microscopic levels. In tooth germs at cap stage, Periostin immunoreactivity was recognizable in the interface between inner enamel epithelium and preodontoblasts as well as in the mesenchymal tissues around cervical loop. Dental follicles around tooth germs at bell stage localized Periostin immunopositivity in addition to the immunopositive areas observed in cap-staged tooth germs, although the functional significance of Periostin has remained unclear in tooth development. Furthermore, Periostin immunoreactivity was also found in the alveolar bone surface. In the incisors of both 7- and 21-day-old mice, immunoreaction for Periostin was discernible in the lingual periodontal ligament and labial fibrous tissue adjacent to the papillary layer. After postnatal day 7, immunoreaction for Periostin came to be restricted to the fibrous bundles in the periodontal ligament in accordance with the organization of the periodontal fibers, indicating its localization matched the morphogenesis of the periodontal ligament. Immunoelectron microscopic observation of the mature periodontal ligament verified the localization of Periostin between the cytoplasmic processes of periodontal fibroblasts and cementoblasts and the adjacent collagen fibrils. Our findings suggest that Periostin is involved at the sites of the cell-to-matrix interaction, serving as adhesive equipment for bearing mechanical forces, including occlusal force and tooth eruption.
Hector F Rios - One of the best experts on this subject based on the ideXlab platform.
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Periostin increases migration and proliferation of human periodontal ligament fibroblasts challenged by tumor necrosis factor α and porphyromonas gingivalis lipopolysaccharides
Journal of Periodontal Research, 2014Co-Authors: Miguel Padialmolina, Sarah L Volk, Hector F RiosAbstract:Background In the chronic established periodontal lesion, the proliferation and migration potential of periodontal ligament (PDL) cells are significantly compromised. Thus, the progressive loss of tissue integrity is favored and normal healing and regeneration compromised. Periostin, a known PDL marker, modulates cell–matrix interactions, cell behavior, as well as the matrix biomechanics and PDL homeostasis. Objective To evaluate whether Periostin restores the regenerative potential of PDL cells in terms of proliferation, migration, and activation of survival signaling pathways after being challenged by Porphyromonas gingivalis lipopolysaccharides and tumor necrosis factor alpha α. Methods Human PDL (hPDL) cells were cultured under different conditions: control, Periostin (50 or 100 ng/mL), and fibroblast growth factor 2 (10 ng/mL) to evaluate cell proliferation (by Ki67), cell migration (by scratch assays) and PI3K/AKT/mTOR pathway activation (by western blot analyses of total AKT, phospho-AKT and PS6). A different set of cultures was challenged by adding tumor necrosis factor alpha α (10 ng/mL) and P. gingivalis lipopolysaccharides (200 ng/mL) to evaluate the effects of Periostin as described above. Results Periostin significantly increased cell proliferation (twofold), migration (especially at earlier time points and low dose) and activation of survival signaling pathway (higher phosphorylation of AKT and PS6). Furthermore, Periostin promoted similar cellular effects even after being challenged with proinflammatory cytokines and bacterial virulence factors. Conclusion Periostin acts as an important modulator of hPDL cell–matrix dynamics. It modulates hPDL proliferation, migration and PI3K/AKT/mTOR pathway. It also helps in overcoming the altered biological phenotype that chronic exposure to periodontal pathogens and proinflammatory cytokines produce in hPDL cells.
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Periostin responds to mechanical stress and tension by activating the mtor signaling pathway
PLOS ONE, 2013Co-Authors: Luciana K Rossellimurai, Luciana O Almeida, Chiara Zagni, Pablo Galindomoreno, Miguel Padialmolina, Sarah L Volk, Marcelo J Murai, Hector F Rios, Cristiane H Squarize, Rogerio M CastilhoAbstract:Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade.
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tumor necrosis factor α and porphyromonas gingivalis lipopolysaccharides decrease Periostin in human periodontal ligament fibroblasts
Journal of Periodontology, 2013Co-Authors: Miguel Padialmolina, Pablo Galindomoreno, Sarah L Volk, Juan C Rodriguez, Julie T Marchesan, Hector F RiosAbstract:Background: Periostin is a matricellular protein essential for tissue integrity and maturation and is believed to have a key function as a modulator of periodontal ligament (PDL) homeostasis. The aim of this study is to evaluate whether periodontal disease-associated pathogen-related virulence factors (endotoxins/lipopolysaccharides [LPS]) and proinflammatory cytokines alter the expression of Periostin in PDL cells.Methods: Human PDL cultures were exposed to inflammatory mediators (tumor necrosis factor-α [TNF-α]), bacterial virulence factors (Porphyromonas gingivalis LPS) or a combination in a biomechanically challenged environment. Culture conditions were applied for 24 hours, 4 days, and 7 days. Periostin and TGF-β inducible gene clone H3 (βIGH3) mRNA expression from cell lysates were analyzed. Periostin and βIGH3 proteins were also detected and semiquantified in both cell lysates and cell culture supernatants by Western blot. In addition, Periostin localization by immunofluorescence was performed. Ana...
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Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice
Journal of Periodontology, 2008Co-Authors: Hector F Rios, Yixia Xie, William V Giannobile, Lynda F Bonewald, S P Conway, Jian Q FengAbstract:Background: The ability of the periodontal ligament (PDL) to absorb and distribute forces is necessary for periodontal homeostasis. This adaptive response may be determined, in part, by a key molecule, Periostin, which maintains the integrity of the PDL during occlusal function and inflammation. Periostin is primarily expressed in the PDL and is highly homologous to βig-H3 (transforming growth factor-beta [TGF-β] inducible gene). Cementum, alveolar bone, and the PDL of Periostin-null mice dramatically deteriorate following tooth eruption. The purpose of this study was to determine the role of Periostin in maintaining the functional integrity of the periodontium.Methods: The periodontia from Periostin-null mice were characterized followed by unloading the incisors. The effect of substrate stretching on Periostin expression was evaluated using a murine PDL cell line. Real-time reverse transcription-polymerase chain reaction was used to quantify mRNA levels of Periostin and TGF-β. TGF-β1 neutralizing antibod...
Miguel Padialmolina - One of the best experts on this subject based on the ideXlab platform.
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Periostin increases migration and proliferation of human periodontal ligament fibroblasts challenged by tumor necrosis factor α and porphyromonas gingivalis lipopolysaccharides
Journal of Periodontal Research, 2014Co-Authors: Miguel Padialmolina, Sarah L Volk, Hector F RiosAbstract:Background In the chronic established periodontal lesion, the proliferation and migration potential of periodontal ligament (PDL) cells are significantly compromised. Thus, the progressive loss of tissue integrity is favored and normal healing and regeneration compromised. Periostin, a known PDL marker, modulates cell–matrix interactions, cell behavior, as well as the matrix biomechanics and PDL homeostasis. Objective To evaluate whether Periostin restores the regenerative potential of PDL cells in terms of proliferation, migration, and activation of survival signaling pathways after being challenged by Porphyromonas gingivalis lipopolysaccharides and tumor necrosis factor alpha α. Methods Human PDL (hPDL) cells were cultured under different conditions: control, Periostin (50 or 100 ng/mL), and fibroblast growth factor 2 (10 ng/mL) to evaluate cell proliferation (by Ki67), cell migration (by scratch assays) and PI3K/AKT/mTOR pathway activation (by western blot analyses of total AKT, phospho-AKT and PS6). A different set of cultures was challenged by adding tumor necrosis factor alpha α (10 ng/mL) and P. gingivalis lipopolysaccharides (200 ng/mL) to evaluate the effects of Periostin as described above. Results Periostin significantly increased cell proliferation (twofold), migration (especially at earlier time points and low dose) and activation of survival signaling pathway (higher phosphorylation of AKT and PS6). Furthermore, Periostin promoted similar cellular effects even after being challenged with proinflammatory cytokines and bacterial virulence factors. Conclusion Periostin acts as an important modulator of hPDL cell–matrix dynamics. It modulates hPDL proliferation, migration and PI3K/AKT/mTOR pathway. It also helps in overcoming the altered biological phenotype that chronic exposure to periodontal pathogens and proinflammatory cytokines produce in hPDL cells.
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Periostin responds to mechanical stress and tension by activating the mtor signaling pathway
PLOS ONE, 2013Co-Authors: Luciana K Rossellimurai, Luciana O Almeida, Chiara Zagni, Pablo Galindomoreno, Miguel Padialmolina, Sarah L Volk, Marcelo J Murai, Hector F Rios, Cristiane H Squarize, Rogerio M CastilhoAbstract:Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade.
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tumor necrosis factor α and porphyromonas gingivalis lipopolysaccharides decrease Periostin in human periodontal ligament fibroblasts
Journal of Periodontology, 2013Co-Authors: Miguel Padialmolina, Pablo Galindomoreno, Sarah L Volk, Juan C Rodriguez, Julie T Marchesan, Hector F RiosAbstract:Background: Periostin is a matricellular protein essential for tissue integrity and maturation and is believed to have a key function as a modulator of periodontal ligament (PDL) homeostasis. The aim of this study is to evaluate whether periodontal disease-associated pathogen-related virulence factors (endotoxins/lipopolysaccharides [LPS]) and proinflammatory cytokines alter the expression of Periostin in PDL cells.Methods: Human PDL cultures were exposed to inflammatory mediators (tumor necrosis factor-α [TNF-α]), bacterial virulence factors (Porphyromonas gingivalis LPS) or a combination in a biomechanically challenged environment. Culture conditions were applied for 24 hours, 4 days, and 7 days. Periostin and TGF-β inducible gene clone H3 (βIGH3) mRNA expression from cell lysates were analyzed. Periostin and βIGH3 proteins were also detected and semiquantified in both cell lysates and cell culture supernatants by Western blot. In addition, Periostin localization by immunofluorescence was performed. Ana...
Lan Bo Chen - One of the best experts on this subject based on the ideXlab platform.
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Periostin induction in tumor cell line explants and inhibition of in vitro cell growth by anti Periostin antibodies
Carcinogenesis, 2005Co-Authors: Lan Bo ChenAbstract:: Several factors have been shown to promote the growth of colorectal cancers. Here, we provide evidence that Periostin, a protein with structural and sequence homology with a TGF-beta-inducible gene, beta ig-h3, is upregulated in colorectal cancers and their liver metastasis, and it may play a role in promoting growth in these tumors. In vitro studies reveal that Periostin promotes growth and cell proliferation in colorectal cancers and that this effect can be abrogated with antibodies to Periostin. Furthermore, exposure of colorectal cancer cells to anti-Periostin antibodies activates apoptosis and potentiates the effects of 5-fluorouracil chemotherapy. The results demonstrate the growth-promoting properties of Periostin, and a possible role of targeting this protein as a therapeutic option in colorectal cancers.
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serum level of the Periostin a homologue of an insect cell adhesion molecule in thymoma patients
Cancer Letters, 2001Co-Authors: Daniel Auclair, Masanobu Kiriyama, Hidefumi Sasaki, Masahiro Kaji, Ichiro Fukai, Yosuke Yamakawa, Yoshitaka Fujii, Lan Bo ChenAbstract:Abstract Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of Periostin. We investigated the serum Periostin level in thymoma patients, and attempted to determine the correlation between serum Periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January 1994 and July 1996. Serum Periostin levels were not significantly different between the thymoma patients (1264.4±122.9 ng/ml) and the normal control (962.0±118.6 ng/ml) ( P =0.0877). There was no relationship between serum Periostin level and age, gender or pathological subtype. However the serum Periostin level of stage IV patients (1497.0±285.8 ng/ml) was significantly higher than normal control ( P =0.0460). These data suggest that serum Periostin level may indicate tumor invasion and progression of thymoma.
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serum level of the Periostin a homologue of an insect cell adhesion molecule as a prognostic marker in nonsmall cell lung carcinomas
Cancer, 2001Co-Authors: M Hidefumi D Sasaki, Daniel Auclair, M Ichiro D Fukai, Masanobu Kiriyama, M Yosuke D Yamakawa, M Yoshitaka D Fujii, Lan Bo ChenAbstract:BACKGROUND Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end, which suggests that it is a secreted protein. Recently, the authors developed a novel sandwich chemiluminescence assay to determine serum concentrations of Periostin. METHODS The authors investigated the serum Periostin level in lung carcinoma patients and attempted to determine the influence of serum Periostin level on clinical outcome for patients with nonsmall cell lung carcinoma (NSCLC) who had undergone surgery between January 1994 and July 1996. Expression of Periostin messenger RNA was also examined by in situ RNA hybridization for lung carcinomas. RESULTS The Periostin gene was shown to be highly expressed at the tumor periphery of lung carcinoma tissue but not within the tumor by in situ RNA hybridization. Serum Periostin levels were not significantly different between the NSCLC patients (1142.1 ± 89.2 ng/mL) and the normal control (962.0 ± 118.6 ng/mL) (P = 0.2985). There was no relation between serum Periostin level and gender, stage, bone metastasis, N status, or T status. However, the serum Periostin levels of NSCLC patients had decreased significantly by 4 weeks after the resection of the tumor. The NSCLC patients with high Periostin level (> 962 ng/mL) had significantly poorer survival than the patients with normal Periostin level (P = 0.0406). Using the Cox proportional hazards regression model, the authors found that stage (P < 0.0001) and serum Periostin level (P = 0.0226) were independent prognostic factors. CONCLUSIONS The in situ RNA hybridization data from the current study suggested that expression of Periostin may be involved in tumor invasionand that the serum Periostin level may serve as a prognostic marker for NSCLC. Cancer 2001;92:843–8. © 2001 American Cancer Society.
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expression of Periostin homologous with an insect cell adhesion molecule as a prognostic marker in non small cell lung cancers
Japanese Journal of Cancer Research, 2001Co-Authors: Hidefumi Sasaki, Daniel Auclair, Lan Bo Chen, Ichiro Fukai, Yoshiaki Nakashima, Satoru Moriyama, Carmen Tam, Massimo Loda, Yoshitaka FujiiAbstract:We used our palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique to identify and isolate a gene, designated Periostin, from cancer tissues and found it to be overexpressed in several human tumors. We attempted to determine the influence of Periostin expression on clinical outcome in patients with non-small cell lung cancer (NSCLC) by reverse transcriptase (RT)-PCR analysis. Periostin gene was highly expressed at the tumor periphery of lung cancer tissue but not within the tumor by in situ RNA hybridization, suggesting that expression of Periostin may be involved in the process of tumor invasion. Periostin transcripts were detected in 50 (49.0%) of the tumor samples, although some paired normal lung samples showed weak expression. There was no relationship between Periostin gene expression and gender, N- or T-status. The NSCLC patients with Periostin expression had significantly poorer survival than the patients without Periostin expression (P = 0.0338).
N.r Lemoine - One of the best experts on this subject based on the ideXlab platform.
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Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia induced cell death role of the beta4 integrin and the pi3k pathway
Oncogene, 2007Co-Authors: P Baril, R Gangeswaran, P.c Mahon, K Caulee, H.m Kocher, T Harada, M Zhu, H Kalthoff, Tatjana Crnogoracjurcevic, N.r LemoineAbstract:Pancreatic ductal adenocarcinoma is a devastating disease, characterized by a rapid progression and poor treatment response. Using gene expression profiling of pancreatic cancer tissues, we previously identified Periostin as a potential diagnostic and therapeutic target. In this study, we report the overexpression of Periostin in a larger set of pancreatic cancer tissues and show that although the Periostin transcript is exclusively expressed in tumour cells, the protein product is only detected in the extracellular matrix adjacent to cancer cells. Using an enzyme-linked immunosorbent assay (ELISA) assay, we show significantly increased levels of Periostin in the sera of pancreatic cancer patients compared to non-cancer controls. We demonstrate that Periostin promotes the invasiveness of tumour cells by increasing the motility of cells without inducing expression of proteases, and enhances the survival of tumour cells exposed to hypoxic conditions. At the molecular level, we provide evidence that the alpha(6)beta(4) integrin complex acts as the cell receptor of Periostin in pancreatic cancer cells and that interaction promotes phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT) though activation of the PI3 kinase pathway, but not the RAS/MEK/ERK pathway. These findings suggest an important role of Periostin in pancreatic cancer and provide a rationale to study Periostin for diagnostic and therapeutic applications.
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Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway
Oncogene, 2007Co-Authors: P Baril, R Gangeswaran, P.c Mahon, K Caulee, H.m Kocher, T Harada, M Zhu, H Kalthoff, T Crnogorac-jurcevic, N.r LemoineAbstract:Pancreatic ductal adenocarcinoma is a devastating disease, characterized by a rapid progression and poor treatment response. Using gene expression profiling of pancreatic cancer tissues, we previously identified Periostin as a potential diagnostic and therapeutic target. In this study, we report the overexpression of Periostin in a larger set of pancreatic cancer tissues and show that although the Periostin transcript is exclusively expressed in tumour cells, the protein product is only detected in the extracellular matrix adjacent to cancer cells. Using an enzyme-linked immunosorbent assay (ELISA) assay, we show significantly increased levels of Periostin in the sera of pancreatic cancer patients compared to non-cancer controls. We demonstrate that Periostin promotes the invasiveness of tumour cells by increasing the motility of cells without inducing expression of proteases, and enhances the survival of tumour cells exposed to hypoxic conditions. At the molecular level, we provide evidence that the alpha(6)beta(4) integrin complex acts as the cell receptor of Periostin in pancreatic cancer cells and that interaction promotes phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT) though activation of the PI3 kinase pathway, but not the RAS/MEK/ERK pathway. These findings suggest an important role of Periostin in pancreatic cancer and provide a rationale to study Periostin for diagnostic and therapeutic applications.
