TY - JOUR
T1 - Endostatin inhibits adhesion of endothelial cells to collagen I via α2β1 integrin, a possible cause of prevention of chondrosarcoma growth
AU - Furumatsu, Takayuki
AU - Yamaguchi, Noriko
AU - Nishida, Keiichiro
AU - Kawai, Akira
AU - Kunisada, Toshiyuki
AU - Namba, Masayoshi
AU - Inoue, Hajime
AU - Ninomiya, Yoshifumi
N1 - Funding Information:
Many endogenous anti-angiogenic molecules such as angio-statin (1) and endostatin (2) were identified recently. Endostatin, which was first purified from a mouse hemangio-endothelioma, is a C-terminal fragment of collagen XVHI (3). Similar anti-angiogenic factors also derived from basement membrane collagens include restm (4), and the non-collagenous domains of the a2(IV), a3(IV) and a6(IV) 1This work was supported in part by Grants-in-Aid for Scientific Research, 11470274 (YN),fromthe Japan Society for the Promotion of Science, and for Special Project Research on Cancer Bioscience, 13216035 (NY), and for Scientific Research, 12671146 (NY), from th2 e Ministry of Education, Science, Sports and Culture of Japan To whom correspondence should be addressed Phone +81-86-235-7127, Fax. +81-86-222-7768, E-mail: yoshinm@cc.okayama-u acjp Abbreviations bFGF, basic fibroblast growth factor, DMEM, Dul-becco's modified Eagle's medium, ECM, extracellular matrix, FITC, fluorescein lsotmocyanate; HUVECs, human umbilical vein endot-hehal cells, LSGS, low serum growth supplement, M200S, Medium 200S, M ^ W4,5-dmeavlthiazol-2-yl)-2,Miphenyl tetrasodium bromide, PBS, phosphate-buffered saline, rh-, recombinant human, RT-PCR, reverse transcnptase-PCR, VEGF, vascular endothelial growth factor
PY - 2002
Y1 - 2002
N2 - Endostatin derived from collagen XVIII is a potent endogenous anti-angiogenic factor that induces regression of various tumors of epithelial origin. Endostatin has been shown to inhibit endothelial cell functions, however, its effect remains controversial. We first attempted here to apply the inhibitory effect of recombinant human endostatin on chondrosarcomas, which originate from the mesenchyme, in nude mice. Endostatin induced reduction of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effect on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration on and attachment to collagen I but did not affect the proliferation of endothelial cells. Although the migration of endothelial cells was stimulated by angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence and absence of the stimulants. Moreover, the inhibitory effect against endothelial cell attachment to collagen I was attenuated or modulated in the presence of neutralizing antibodies of α2, α5β1, and αVβ3 integrins but not that of α1 integrin. Our results suggest that endostatin might suppress the α2β1 integrin function of endothelial cells via α5β1 or αVβ3 integrin. We propose here that endostatin might be effective for anti-angiogenic therapy for human chondrosarcomas through the suppression of α2β1 integrin functions in endothelial cells.
AB - Endostatin derived from collagen XVIII is a potent endogenous anti-angiogenic factor that induces regression of various tumors of epithelial origin. Endostatin has been shown to inhibit endothelial cell functions, however, its effect remains controversial. We first attempted here to apply the inhibitory effect of recombinant human endostatin on chondrosarcomas, which originate from the mesenchyme, in nude mice. Endostatin induced reduction of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effect on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration on and attachment to collagen I but did not affect the proliferation of endothelial cells. Although the migration of endothelial cells was stimulated by angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence and absence of the stimulants. Moreover, the inhibitory effect against endothelial cell attachment to collagen I was attenuated or modulated in the presence of neutralizing antibodies of α2, α5β1, and αVβ3 integrins but not that of α1 integrin. Our results suggest that endostatin might suppress the α2β1 integrin function of endothelial cells via α5β1 or αVβ3 integrin. We propose here that endostatin might be effective for anti-angiogenic therapy for human chondrosarcomas through the suppression of α2β1 integrin functions in endothelial cells.
KW - Basic fibroblast growth factor
KW - Chondrosarcoma
KW - Endostatin
KW - Integrin
KW - Tumor angiogenesis
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U2 - 10.1093/oxfordjournals.jbchem.a003142
DO - 10.1093/oxfordjournals.jbchem.a003142
M3 - Article
C2 - 11927001
AN - SCOPUS:0036242559
VL - 131
SP - 619
EP - 626
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 4
ER -