The Experts below are selected from a list of 41853 Experts worldwide ranked by ideXlab platform
Yuji Hiraki - One of the best experts on this subject based on the ideXlab platform.
-
expression of the cartilage derived anti Angiogenic Factor chondromodulin i decreases in the early stage of experimental osteoarthritis
The Journal of Rheumatology, 2003Co-Authors: Tadashi Hayami, Haruko Funaki, Kiyoshi Yaoeda, Yuji Hiraki, Kaori Mitui, Kunihiko Tokunaga, Jun Kondo, Hiroshi Hatano, Hiroshi Yamagiwa, Tadashi YamamotoAbstract:OBJECTIVE: Chondromodulin-I (ChM-I), a cartilage derived anti-Angiogenic Factor, has been shown to regulate the vascular invasion during endochondral bone formation. We evaluated the expression and localization of ChM-I in articular cartilage during the progression of osteoarthritis (OA) in the rat, and correlated ChM-I expression with the increase in vascular invasion into OA articular cartilage. METHODS: Expression of ChM-I, type II collagen, basic fibroblast growth Factor, vascular endothelial growth Factor (VEGF), and matrix metalloproteinases MMP-9 and MMP-13 were examined in articular cartilage of intact growing and adult rats and in the surgically induced OA model using in situ hybridization, Western blot analysis, and immunohistochemistry. Co-immunostaining for ChM-I and CD-31 was performed to localize ChM-I and neovascularization in articular cartilage at advanced stage of OA. RESULTS: Abundant expression of ChM-I protein was detected in avascular regions of the developing and adult healthy articular cartilage. In early OA, ChM-I expression decreased in the superficial zone of articular cartilage, while levels of proteoglycan and type II collagen were comparable to control. In advanced OA, ChM-I expression was reduced in all zones of articular cartilage, and the number of VEGF-expressing cells was increased. Immunohistochemical studies showed that vascular invasion occurred in proximity to chondrocytes with high expression of pro-Angiogenic markers, and decreased expression of ChM-I. CONCLUSION: High expression of ChM-I was detected in articular cartilage of growing and normal adult joints, implicating its role in the maintenance of avascularity of intact articular cartilage. Expression of ChM-I decreased, while expression of VEGF and other pro-Angiogenic Factors increased, in OA cartilage. These findings suggest the loss of ChM-I from articular cartilage might be responsible in part for promoting blood vessel invasion into the cartilage during progression of OA.
-
role of cartilage derived anti Angiogenic Factor chondromodulin i during endochondral bone formation
Osteoarthritis and Cartilage, 2001Co-Authors: Chisa Shukunami, Yuji HirakiAbstract:Abstract Objective Cartilage is a typical avasclar tissue that exhibits powerful resistance to angiogenesis or vascular invasion. We previously identified a cartilage-specific 25kDa glycosylated protein, chondromodulin-I (ChM-I), as anti-Angiogenic Factor. Taking advantage of ectopic bone formation and xenograft tumour model by human chondrosarcoma cell line OUMS-27, we examined how ChM-I is involved in switching of angiogenesis in cartilage. Design Gene expression pattern of ChM-I was examined in 4-week-old mice and mouse embryos by northern blot analysis and in situ hybridization. To evaluate the effect of ChM-I on ectopic bone formation, guanidine extracts of demineralized bone matrix were mixed with the ChM-I-bound heparin-Sepharose beads and were implanted onto the fasciae of back muscle of 6-week old nude mice. To analyse the effect of ChM-I on tumour angiogenesis, the level of ChM-I mRNA in cartilaginous tumours was assessed by competitive PCR, and compared with that of articular cartilage. Then, human chondrosarcoma OUMS-27 cells were inoculated into the back of nude mice to form a tumour about 45mm 3 in size. Recombinant ChM-I protein was administrated into OUMS-27 xenograft tumours for the initial 5 days to study its effect against tumour-angiogenesis. Results ChM-I gene was specifically expressed in cartilage of 4-week-old mice. Eye and thymus were also identified as minor expression sites. However, during endochondral bone development, cartilage changes its character from anti-Angiogenic into Angiogenic prior to the replacement of calcified cartilage by bone. In embryos, ChM-I mRNA was expressed in proliferative and upper hypertrophic cartilage zones in the developing cartilaginous bone rudiments, but completely abolished in lower hypertrophic and calcified cartilage zones. Purified ChM-I protein apparently inhibited vascular invasion into cartilage induced by the implantation of demineralized bone matrix in nude mice, leading to the inhibition of replacement of cartilage. The level of ChM-I transcripts in the lower-grade chondrosarcomas was substantially reduced to several hundreds or less in the lower-grade chondrosarcomas, compared with that of articular cartilage or other benign cartilage tumours. The local administration of recombinant human ChM-I almost completely blocked tumour angiogenesis and growth in the human chondrosarcoma xenografts in mice. Conclusions ChM-I is involved in the anti-Angiogenic property of cartilage and its absence creates a permissive microenvironment for vascular invasion into cartilage under physiological and pathological conditions.
Tadashi Hayami - One of the best experts on this subject based on the ideXlab platform.
-
chondromodulin 1 directly suppresses growth of human cancer cells
BMC Cancer, 2009Co-Authors: Hisashi Mera, Tatsuya Yoshizawa, Osamu Ishibashi, Tadashi Hayami, Hiroshi Kitahara, Hiroyuki Kawashima, Akira Ogose, Naoki Kondo, Hiroshi Yamagiwa, Naoto EndoAbstract:Background Chondromodulin-1 (ChM1), an endogenous anti-Angiogenic Factor expressed in cartilage, has been suggested to inhibit invasion of endothelial cells into cartilage. In addition, the ectopic administration of ChM1 has been reported to suppress tumorigenesis in vivo. However, it is unclear whether the anti-tumor effect is due to not only the anti-vascularization effect of ChM1, but also its direct action against oncocytes. In the present study, we sought to determine whether ChM1 has a direct action on tumor cells.
-
expression of the cartilage derived anti Angiogenic Factor chondromodulin i decreases in the early stage of experimental osteoarthritis
The Journal of Rheumatology, 2003Co-Authors: Tadashi Hayami, Haruko Funaki, Kiyoshi Yaoeda, Yuji Hiraki, Kaori Mitui, Kunihiko Tokunaga, Jun Kondo, Hiroshi Hatano, Hiroshi Yamagiwa, Tadashi YamamotoAbstract:OBJECTIVE: Chondromodulin-I (ChM-I), a cartilage derived anti-Angiogenic Factor, has been shown to regulate the vascular invasion during endochondral bone formation. We evaluated the expression and localization of ChM-I in articular cartilage during the progression of osteoarthritis (OA) in the rat, and correlated ChM-I expression with the increase in vascular invasion into OA articular cartilage. METHODS: Expression of ChM-I, type II collagen, basic fibroblast growth Factor, vascular endothelial growth Factor (VEGF), and matrix metalloproteinases MMP-9 and MMP-13 were examined in articular cartilage of intact growing and adult rats and in the surgically induced OA model using in situ hybridization, Western blot analysis, and immunohistochemistry. Co-immunostaining for ChM-I and CD-31 was performed to localize ChM-I and neovascularization in articular cartilage at advanced stage of OA. RESULTS: Abundant expression of ChM-I protein was detected in avascular regions of the developing and adult healthy articular cartilage. In early OA, ChM-I expression decreased in the superficial zone of articular cartilage, while levels of proteoglycan and type II collagen were comparable to control. In advanced OA, ChM-I expression was reduced in all zones of articular cartilage, and the number of VEGF-expressing cells was increased. Immunohistochemical studies showed that vascular invasion occurred in proximity to chondrocytes with high expression of pro-Angiogenic markers, and decreased expression of ChM-I. CONCLUSION: High expression of ChM-I was detected in articular cartilage of growing and normal adult joints, implicating its role in the maintenance of avascularity of intact articular cartilage. Expression of ChM-I decreased, while expression of VEGF and other pro-Angiogenic Factors increased, in OA cartilage. These findings suggest the loss of ChM-I from articular cartilage might be responsible in part for promoting blood vessel invasion into the cartilage during progression of OA.
Ruth Lupu - One of the best experts on this subject based on the ideXlab platform.
-
the Angiogenic Factor cyr61 in breast cancer molecular pathology and therapeutic perspectives
Endocrine-related Cancer, 2003Co-Authors: Javier A Menendez, Inderjit Mehmi, David W Griggs, Ruth LupuAbstract:CYR61 (CNN1), a member of the cysteine rich 61/connective tissue growth Factor/nephroblastoma overexpressed (CYR61/CTFG/NOV) family of growth regulators (CNN), is a pro-Angiogenic Factor that mediates diverse roles in development, cell proliferation, and tumorigenesis. We have recently shown that CYR61 is overexpressed in invasive and metastatic human breast cancer cells. Accordingly, elevated levels of CYR61 in breast cancer are associated with more advanced disease. Unfortunately, the exact mechanisms by which CYR61 promotes an aggressive breast cancer phenotype are still largely unknown. This review examines the functional role of CYR61 in breast cancer disease, presenting evidence that CYR61 signaling may play a major role in estrogen- as well as growth Factor-dependent breast cancer progression. We also emphasize the functional significance of the molecular connection of CYR61 and its integrin receptor alpha(v)beta(3) enhancing breast cancer aggressiveness. Moreover, we describe experimental evidence that establishes a novel role for CYR61 determining the protection of human breast cancer cells against chemotherapy-induced apoptosis through its interactions with the integrin receptor alpha(v)beta(3). All these findings delineate a new noteworthy function of a CYR61/alpha(v)beta(3) autocrine-paracrine signaling pathway within both angiogenesis and breast cancer progression, which would allow a dual anti-Angiogenic and anti-tumor benefit with a single drug.
-
expression and function of cyr61 an Angiogenic Factor in breast cancer cell lines and tumor biopsies
Cancer Research, 2000Co-Authors: Miaw Sheue Tsai, Ann E Hornby, Johnathon Lakins, Ruth LupuAbstract:We have previously shown that expression of heregulin (HRG) is closely correlated with breast cancer progression. We have subsequently isolated Cyr61, a ligand for the alpha(v)beta3 integrin that is differentially expressed in HRG-positive cells, and have shown that it is expressed in all of the invasive and metastatic breast cancer cell lines tested. Preliminary evaluation of Cyr61 expression in breast tumor biopsies revealed expression of Cyr61 in about 30% of invasive breast carcinomas. Significantly, we demonstrated that Cyr61 is a downstream effector of HRG action, because a Cyr61-neutralizing antibody abolished the ability of HRG-expressing cells to migrate in vitro. Furthermore, we have shown that HRG-expressing cells denote higher levels of alpha(v)beta3 expression, and we have established that Cyr61 action is mediated, at least in part, through its receptor alpha(v)beta3, because a functional blocking antibody of the alpha(v)beta3 blocked the Matrigel outgrowth of HRG-expressing cells. These results strongly suggest that Cyr61 is necessary for HRG-mediated chemomigration and that Cyr61 plays a functional role in breast cancer progression, possibly through its interactions with the alpha(v)beta3 receptor.
Tadashi Yamamoto - One of the best experts on this subject based on the ideXlab platform.
-
expression of the cartilage derived anti Angiogenic Factor chondromodulin i decreases in the early stage of experimental osteoarthritis
The Journal of Rheumatology, 2003Co-Authors: Tadashi Hayami, Haruko Funaki, Kiyoshi Yaoeda, Yuji Hiraki, Kaori Mitui, Kunihiko Tokunaga, Jun Kondo, Hiroshi Hatano, Hiroshi Yamagiwa, Tadashi YamamotoAbstract:OBJECTIVE: Chondromodulin-I (ChM-I), a cartilage derived anti-Angiogenic Factor, has been shown to regulate the vascular invasion during endochondral bone formation. We evaluated the expression and localization of ChM-I in articular cartilage during the progression of osteoarthritis (OA) in the rat, and correlated ChM-I expression with the increase in vascular invasion into OA articular cartilage. METHODS: Expression of ChM-I, type II collagen, basic fibroblast growth Factor, vascular endothelial growth Factor (VEGF), and matrix metalloproteinases MMP-9 and MMP-13 were examined in articular cartilage of intact growing and adult rats and in the surgically induced OA model using in situ hybridization, Western blot analysis, and immunohistochemistry. Co-immunostaining for ChM-I and CD-31 was performed to localize ChM-I and neovascularization in articular cartilage at advanced stage of OA. RESULTS: Abundant expression of ChM-I protein was detected in avascular regions of the developing and adult healthy articular cartilage. In early OA, ChM-I expression decreased in the superficial zone of articular cartilage, while levels of proteoglycan and type II collagen were comparable to control. In advanced OA, ChM-I expression was reduced in all zones of articular cartilage, and the number of VEGF-expressing cells was increased. Immunohistochemical studies showed that vascular invasion occurred in proximity to chondrocytes with high expression of pro-Angiogenic markers, and decreased expression of ChM-I. CONCLUSION: High expression of ChM-I was detected in articular cartilage of growing and normal adult joints, implicating its role in the maintenance of avascularity of intact articular cartilage. Expression of ChM-I decreased, while expression of VEGF and other pro-Angiogenic Factors increased, in OA cartilage. These findings suggest the loss of ChM-I from articular cartilage might be responsible in part for promoting blood vessel invasion into the cartilage during progression of OA.
Hiroshi Yamagiwa - One of the best experts on this subject based on the ideXlab platform.
-
chondromodulin 1 directly suppresses growth of human cancer cells
BMC Cancer, 2009Co-Authors: Hisashi Mera, Tatsuya Yoshizawa, Osamu Ishibashi, Tadashi Hayami, Hiroshi Kitahara, Hiroyuki Kawashima, Akira Ogose, Naoki Kondo, Hiroshi Yamagiwa, Naoto EndoAbstract:Background Chondromodulin-1 (ChM1), an endogenous anti-Angiogenic Factor expressed in cartilage, has been suggested to inhibit invasion of endothelial cells into cartilage. In addition, the ectopic administration of ChM1 has been reported to suppress tumorigenesis in vivo. However, it is unclear whether the anti-tumor effect is due to not only the anti-vascularization effect of ChM1, but also its direct action against oncocytes. In the present study, we sought to determine whether ChM1 has a direct action on tumor cells.
-
expression of the cartilage derived anti Angiogenic Factor chondromodulin i decreases in the early stage of experimental osteoarthritis
The Journal of Rheumatology, 2003Co-Authors: Tadashi Hayami, Haruko Funaki, Kiyoshi Yaoeda, Yuji Hiraki, Kaori Mitui, Kunihiko Tokunaga, Jun Kondo, Hiroshi Hatano, Hiroshi Yamagiwa, Tadashi YamamotoAbstract:OBJECTIVE: Chondromodulin-I (ChM-I), a cartilage derived anti-Angiogenic Factor, has been shown to regulate the vascular invasion during endochondral bone formation. We evaluated the expression and localization of ChM-I in articular cartilage during the progression of osteoarthritis (OA) in the rat, and correlated ChM-I expression with the increase in vascular invasion into OA articular cartilage. METHODS: Expression of ChM-I, type II collagen, basic fibroblast growth Factor, vascular endothelial growth Factor (VEGF), and matrix metalloproteinases MMP-9 and MMP-13 were examined in articular cartilage of intact growing and adult rats and in the surgically induced OA model using in situ hybridization, Western blot analysis, and immunohistochemistry. Co-immunostaining for ChM-I and CD-31 was performed to localize ChM-I and neovascularization in articular cartilage at advanced stage of OA. RESULTS: Abundant expression of ChM-I protein was detected in avascular regions of the developing and adult healthy articular cartilage. In early OA, ChM-I expression decreased in the superficial zone of articular cartilage, while levels of proteoglycan and type II collagen were comparable to control. In advanced OA, ChM-I expression was reduced in all zones of articular cartilage, and the number of VEGF-expressing cells was increased. Immunohistochemical studies showed that vascular invasion occurred in proximity to chondrocytes with high expression of pro-Angiogenic markers, and decreased expression of ChM-I. CONCLUSION: High expression of ChM-I was detected in articular cartilage of growing and normal adult joints, implicating its role in the maintenance of avascularity of intact articular cartilage. Expression of ChM-I decreased, while expression of VEGF and other pro-Angiogenic Factors increased, in OA cartilage. These findings suggest the loss of ChM-I from articular cartilage might be responsible in part for promoting blood vessel invasion into the cartilage during progression of OA.