The Experts below are selected from a list of 64635 Experts worldwide ranked by ideXlab platform
Yoshiharu Sakai - One of the best experts on this subject based on the ideXlab platform.
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loss of smad4 promotes colorectal cancer progression by recruiting tumor associated neutrophils via the cxcl1 8 cxcr2 axis
Clinical Cancer Research, 2019Co-Authors: Ryotaro Ogawa, Hideyo Hirai, Keita Hanada, Yoshiyuki Kiyasu, Gen Nishikawa, Takamasa Yamamoto, Susumu Inamoto, Rei Mizuno, Yoshiro Itatani, Yoshiharu SakaiAbstract:Purpose: SMAD4 is a key transcriptional factor of TGFβ signaling and acts as a tumor suppressor in colorectal cancer. In the present study, we explored the immunologic effect of SMAD4 on the tumor microenvironment. Experimental Design: Using 99 clinical specimens and human colorectal cancer cell lines, we investigate the relationship between SMAD4 expression and neutrophil accumulation. We immunohistochemically analyzed expression of SMAD4, CXCL1, CXCL8, CXCR2, and other proteins with clinical specimens. Finally, we determined the serum levels of CXCL1 and CXCL8 in 125 patients with colorectal cancer. Results: SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2. In turn, when neutrophils were exposed to the supernatant of SMAD4-negative colorectal cancer cells, they produced a large amount of CXCL1 and CXCL8 by themselves in vitro. In human clinical specimens, we found that neutrophil infiltration into the peritumoral stroma was more marked in SMAD4-negative colorectal cancer compared with that in SMAD4-positive colorectal cancer, and that both CXCL1 and CXCL8 were abundantly expressed in the tumor-infiltrating neutrophils. Neutrophils isolated from primary colorectal cancer expressed significantly higher levels of CXCL1 and CXCL8 than did those isolated from peripheral blood. Furthermore, tumor-infiltrating neutrophils expressed MMP2 and MMP9 in addition to ARG1 and IDO. Serum CXCL8 level was significantly higher in colorectal cancer patients, especially those at stage II/III, and statistical analysis indicated a high CXCL8 level was associated with a shorter overall survival and relapse-free survival. Conclusions: Blockade of the CXCL1/8–CXCR2 axis could be a novel therapeutic approach against SMAD4-negative colorectal cancer.
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loss of smad4 promotes colorectal cancer progression by recruiting tumor associated neutrophils via the cxcl1 8 cxcr2 axis
Clinical Cancer Research, 2019Co-Authors: Ryotaro Ogawa, Hideyo Hirai, Keita Hanada, Yoshiyuki Kiyasu, Gen Nishikawa, Takamasa Yamamoto, Susumu Inamoto, Rei Mizuno, Yoshiro Itatani, Yoshiharu SakaiAbstract:Purpose: SMAD4 is a key transcriptional factor of TGFβ signaling and acts as a tumor suppressor in colorectal cancer. In the present study, we explored the immunologic effect of SMAD4 on the tumor microenvironment. Experimental Design: Using 99 clinical specimens and human colorectal cancer cell lines, we investigate the relationship between SMAD4 expression and neutrophil accumulation. We immunohistochemically analyzed expression of SMAD4, CXCL1, CXCL8, CXCR2, and other proteins with clinical specimens. Finally, we determined the serum levels of CXCL1 and CXCL8 in 125 patients with colorectal cancer. Results: SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2. In turn, when neutrophils were exposed to the supernatant of SMAD4-negative colorectal cancer cells, they produced a large amount of CXCL1 and CXCL8 by themselves in vitro. In human clinical specimens, we found that neutrophil infiltration into the peritumoral stroma was more marked in SMAD4-negative colorectal cancer compared with that in SMAD4-positive colorectal cancer, and that both CXCL1 and CXCL8 were abundantly expressed in the tumor-infiltrating neutrophils. Neutrophils isolated from primary colorectal cancer expressed significantly higher levels of CXCL1 and CXCL8 than did those isolated from peripheral blood. Furthermore, tumor-infiltrating neutrophils expressed MMP2 and MMP9 in addition to ARG1 and IDO. Serum CXCL8 level was significantly higher in colorectal cancer patients, especially those at stage II/III, and statistical analysis indicated a high CXCL8 level was associated with a shorter overall survival and relapse-free survival. Conclusions: Blockade of the CXCL1/8–CXCR2 axis could be a novel therapeutic approach against SMAD4-negative colorectal cancer.
Ming Cheng Chen - One of the best experts on this subject based on the ideXlab platform.
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CXCL2 cxcr2 axis induces cancer stem cell characteristics in cpt 11 resistant lovo colon cancer cells via gαi 2 and gαq 11
Journal of Cellular Physiology, 2019Co-Authors: Ming Cheng Chen, Rathinasamy Baskaran, Nien Hung Lee, Hsi Hsien Hsu, Yueh Min Lin, Vijaya Padma Viswanadha, Wei Wen Kuo, Chih Yang HuangAbstract:Cancer stem cells (CSCs) exist in colon cancer and exhibit characteristics of stem cells which are due to lineages of tissues where they arise. Epithelial to mesenchymal transition (EMT)-undergoing cancer cells display CSC properties and therapeutic resistance. Cancer and stromal cells comprise of a tumor microenvironment. One way the two populations communicate with each other is to secret CXC ligands (CXCLs). CXCLs are capable of causing chemotaxis of specific types of stromal cells and control angiogenesis. Double immunofluorescence, western blot analysis, and colony-formation assay were carried out to compare parental and CPT-11-resistant LoVo cells. CPT-11-R LoVo colon cancer cells showed increased expression of CXCL1, CXCL2, CXCL3, and CXCL8. They displayed significantly increased intracellular protein levels of CXCL2 and CXCR2. CPT-11-R LoVo cells showed significantly elevated expression in aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 24 (CD24), cluster of differentiation 44 (CD44), and epithelial cell adhesion molecule (EpCAM). CXCL2 knockdown by short hairpin RNA resulted in reduced expression of CSC proteins, cyclins, EMT markers, G proteins, and matrix metalloproteinases (MMPs). Finally, Gαi-2 was found to promote expression of CSC genes and tumorigenesis which were more apparent in the resistant cells. In addition, Gαq/11 showed a similar pattern with exceptions of EpCAM and MMP9. Therefore, CXCL2-CXCR2 axis mediates through Gαi-2 and Gαq/11 to promote tumorigenesis and contributes to CSC properties of CPT-11-R LoVo cells.
Tatsuro Tamura - One of the best experts on this subject based on the ideXlab platform.
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abstract 6193 the clinicopathologic significance of the cxcr2 ligands cxcl1 CXCL2 cxcl3 cxcl5 cxcl6 cxcl7 and cxcl8 in gastric cancer
Cancer Research, 2020Co-Authors: Yurie Yamamoto, Kenji Kuroda, Tomohiro Sera, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Shingo Togano, Tomohisa Okuno, Mami Yoshii, Tatsuro TamuraAbstract:Background: Cancer progression has been recognized as not only the proliferation of tumor cells but also an interaction between cancer cells and the surrounding stroma in the tumor microenvironment. Among the tumor stromal cells, fibroblasts (especially cancer-associated fibroblasts) have been reported to be closely associated with tumor development in various solid carcinomas. We reported that chemokine (C-X-C motif) receptor 2 (CXCR2) signaling might play an important role in the pathogenic construction of tumor fibroblasts in the gastric tumor microenvironment, suggesting that gastric cancer cells might alter their adjacent stroma to form a permissive environment for tumor progression. Following those findings, we reported that chemokine (C-X-C motif) ligand 1 (CXCL1) from cells stimulated the recruitment of bone marrow cells into the gastric cancer (GC) microenvironment via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling, resulting in the malignant progression of GC. The reported CXCR2 ligands are not only CXCL1 but also CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8. However, there has been only a single in vitro study of significance of these CXCR2 ligands in GC. We thus examined the clinicopathological significance of these members of the CXCL family in GC. Method: We retrospectively analyzed the cases of 590 GC patients. The expressions of CXCR2 ligands were investigated by immunohistochemistry, and we then analyzed the correlation between the clinicopathological features of the patients and the expressions of CXCR2 ligands. Result: The expressions were as follows: CXCL1, 46.2% (257/557); CXCL2, 20.7% (122/590); CXCL3, 17.1% (101/589); CXCL5/CXCL6, 2.9% (17/589); CXCL7, 36.4% (215/590); and CXCL8 1.7% (10/585) of the cases. High invasion depth was correlated with CXCL1 expression. Lymph node metastasis was correlated with high expressions of CXCL1 and CXCL7. Lymphatic invasion and venous invasion were correlated with CXCL1 and CXCL7 expression. Peritoneal cytology positivity was correlated with high expressions of CXCL1 and CXCL7. The prognoses of the CXCL1-positive patients were significantly poorer than those of the CXCL1-negative patients (p Conclusion: Among the CXCR2 ligands, CXCL1 and CXCL7 were frequently expressed in GC cells. CXCL1 was closely associated with malignant potential of GC and was an independent prognostic factor. CXCL1 might play an important role in the malignant progression of GC via CXCL1/CXCR2 signaling. Citation Format: Yurie Yamamoto, Kenji Kuroda, Tomohiro Sera, Atsushi Sugimoto, Syuhei Kushiyama, Sadaaki Nishimura, Shingo Togano, Tomohisa Okuno, Mami Yoshii, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Masakazu Yashiro. The clinicopathologic significance of the CXCR2 ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6193.
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the clinicopathological significance of the cxcr2 ligands cxcl1 CXCL2 cxcl3 cxcl5 cxcl6 cxcl7 and cxcl8 in gastric cancer
Anticancer Research, 2019Co-Authors: Yurie Yamamoto, Kenji Kuroda, Tomohiro Sera, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Shingo Togano, Tomohisa Okuno, Mami Yoshii, Tatsuro TamuraAbstract:BACKGROUND/AIM We have previously reported that chemokine (C-X-C motif) receptor 2 (CXCR2) signaling was associated with the malignant progression of gastric cancer (GC). We thus examined the clinicopathological significance of CXCR2 ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8, in GC. PATIENTS AND METHODS The expression of CXCR2 ligands in 590 GC cases was investigated by immunohistochemistry. RESULTS The expression was as follows: CXCL1, 46.2% (257/557); CXCL2, 20.7% (122/590); CXCL3, 17.1% (101/589); CXCL5/CXCL6, 2.9% (17/589); CXCL7, 36.4% (215/590); and CXCL8 1.7% (10/585) of the cases. High invasion depth was correlated with CXCL1 expression. Lymph node metastasis and peritoneal cytology positivity were correlated with high expression of CXCL1 and CXCL7. The prognoses of the CXCL1-positive patients were significantly poorer than those of the CXCL1-negative patients (p<0.001). CONCLUSION Among the CXCR2 ligands, CXCL7 and especially CXCL1, might play an important role in the malignant progression of GC via CXCR2 signaling.
Ryotaro Ogawa - One of the best experts on this subject based on the ideXlab platform.
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loss of smad4 promotes colorectal cancer progression by recruiting tumor associated neutrophils via the cxcl1 8 cxcr2 axis
Clinical Cancer Research, 2019Co-Authors: Ryotaro Ogawa, Hideyo Hirai, Keita Hanada, Yoshiyuki Kiyasu, Gen Nishikawa, Takamasa Yamamoto, Susumu Inamoto, Rei Mizuno, Yoshiro Itatani, Yoshiharu SakaiAbstract:Purpose: SMAD4 is a key transcriptional factor of TGFβ signaling and acts as a tumor suppressor in colorectal cancer. In the present study, we explored the immunologic effect of SMAD4 on the tumor microenvironment. Experimental Design: Using 99 clinical specimens and human colorectal cancer cell lines, we investigate the relationship between SMAD4 expression and neutrophil accumulation. We immunohistochemically analyzed expression of SMAD4, CXCL1, CXCL8, CXCR2, and other proteins with clinical specimens. Finally, we determined the serum levels of CXCL1 and CXCL8 in 125 patients with colorectal cancer. Results: SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2. In turn, when neutrophils were exposed to the supernatant of SMAD4-negative colorectal cancer cells, they produced a large amount of CXCL1 and CXCL8 by themselves in vitro. In human clinical specimens, we found that neutrophil infiltration into the peritumoral stroma was more marked in SMAD4-negative colorectal cancer compared with that in SMAD4-positive colorectal cancer, and that both CXCL1 and CXCL8 were abundantly expressed in the tumor-infiltrating neutrophils. Neutrophils isolated from primary colorectal cancer expressed significantly higher levels of CXCL1 and CXCL8 than did those isolated from peripheral blood. Furthermore, tumor-infiltrating neutrophils expressed MMP2 and MMP9 in addition to ARG1 and IDO. Serum CXCL8 level was significantly higher in colorectal cancer patients, especially those at stage II/III, and statistical analysis indicated a high CXCL8 level was associated with a shorter overall survival and relapse-free survival. Conclusions: Blockade of the CXCL1/8–CXCR2 axis could be a novel therapeutic approach against SMAD4-negative colorectal cancer.
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loss of smad4 promotes colorectal cancer progression by recruiting tumor associated neutrophils via the cxcl1 8 cxcr2 axis
Clinical Cancer Research, 2019Co-Authors: Ryotaro Ogawa, Hideyo Hirai, Keita Hanada, Yoshiyuki Kiyasu, Gen Nishikawa, Takamasa Yamamoto, Susumu Inamoto, Rei Mizuno, Yoshiro Itatani, Yoshiharu SakaiAbstract:Purpose: SMAD4 is a key transcriptional factor of TGFβ signaling and acts as a tumor suppressor in colorectal cancer. In the present study, we explored the immunologic effect of SMAD4 on the tumor microenvironment. Experimental Design: Using 99 clinical specimens and human colorectal cancer cell lines, we investigate the relationship between SMAD4 expression and neutrophil accumulation. We immunohistochemically analyzed expression of SMAD4, CXCL1, CXCL8, CXCR2, and other proteins with clinical specimens. Finally, we determined the serum levels of CXCL1 and CXCL8 in 125 patients with colorectal cancer. Results: SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2. In turn, when neutrophils were exposed to the supernatant of SMAD4-negative colorectal cancer cells, they produced a large amount of CXCL1 and CXCL8 by themselves in vitro. In human clinical specimens, we found that neutrophil infiltration into the peritumoral stroma was more marked in SMAD4-negative colorectal cancer compared with that in SMAD4-positive colorectal cancer, and that both CXCL1 and CXCL8 were abundantly expressed in the tumor-infiltrating neutrophils. Neutrophils isolated from primary colorectal cancer expressed significantly higher levels of CXCL1 and CXCL8 than did those isolated from peripheral blood. Furthermore, tumor-infiltrating neutrophils expressed MMP2 and MMP9 in addition to ARG1 and IDO. Serum CXCL8 level was significantly higher in colorectal cancer patients, especially those at stage II/III, and statistical analysis indicated a high CXCL8 level was associated with a shorter overall survival and relapse-free survival. Conclusions: Blockade of the CXCL1/8–CXCR2 axis could be a novel therapeutic approach against SMAD4-negative colorectal cancer.
Chih Yang Huang - One of the best experts on this subject based on the ideXlab platform.
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CXCL2 cxcr2 axis induces cancer stem cell characteristics in cpt 11 resistant lovo colon cancer cells via gαi 2 and gαq 11
Journal of Cellular Physiology, 2019Co-Authors: Ming Cheng Chen, Rathinasamy Baskaran, Nien Hung Lee, Hsi Hsien Hsu, Yueh Min Lin, Vijaya Padma Viswanadha, Wei Wen Kuo, Chih Yang HuangAbstract:Cancer stem cells (CSCs) exist in colon cancer and exhibit characteristics of stem cells which are due to lineages of tissues where they arise. Epithelial to mesenchymal transition (EMT)-undergoing cancer cells display CSC properties and therapeutic resistance. Cancer and stromal cells comprise of a tumor microenvironment. One way the two populations communicate with each other is to secret CXC ligands (CXCLs). CXCLs are capable of causing chemotaxis of specific types of stromal cells and control angiogenesis. Double immunofluorescence, western blot analysis, and colony-formation assay were carried out to compare parental and CPT-11-resistant LoVo cells. CPT-11-R LoVo colon cancer cells showed increased expression of CXCL1, CXCL2, CXCL3, and CXCL8. They displayed significantly increased intracellular protein levels of CXCL2 and CXCR2. CPT-11-R LoVo cells showed significantly elevated expression in aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 24 (CD24), cluster of differentiation 44 (CD44), and epithelial cell adhesion molecule (EpCAM). CXCL2 knockdown by short hairpin RNA resulted in reduced expression of CSC proteins, cyclins, EMT markers, G proteins, and matrix metalloproteinases (MMPs). Finally, Gαi-2 was found to promote expression of CSC genes and tumorigenesis which were more apparent in the resistant cells. In addition, Gαq/11 showed a similar pattern with exceptions of EpCAM and MMP9. Therefore, CXCL2-CXCR2 axis mediates through Gαi-2 and Gαq/11 to promote tumorigenesis and contributes to CSC properties of CPT-11-R LoVo cells.
