Son, Hye-Nam Nam, Ju-Ock Kim, Soyoun Kim, In San 2024-01-20T11:30:46Z 2024-01-20T11:30:46Z 2022-01-10 2013-10 0167-4889 https://pubs.kist.re.kr/handle/201004/127567 TGFBI, a transforming growth factor beta-induced extracellular matrix protein, circulates at a level of similar to 300 ng/ml in humans and modulates several integrin-mediated cellular functions. The protein contains an N-terminal EMI domain, four consecutive FAS1 domains, and the RGD motif. Each FAS1 domain and the RGD motif have been known to interact with avb3 integrin. Here, we found that the binding affinity (K-d) of TGFBI for alpha v beta 3 integrin was approximately 3.8 x 10(-8) M, a value similar to 2300-fold higher than that of a single FAS1 domain, and demonstrated that this greater affinity was due to the cooperative action of the four FAS1 domains and the RGD motif. Moreover, TGFBI exhibited more potent anti-angiogenic and anti-tumorigenic activities, even at a 100-fold lower molar dose than the reported effective dose of the FAS1 domain. Finally, our data showed that TGFBI specifically targeted the tumor vasculature and accumulated at the tumor site. Collectively, our results support the theory that TGFBI acts as a potent endogenous anti-tumor and anti-angiogenic molecule by targeting alpha v beta 3 integrin, and highlights the importance of physiological circulating TGFBI levels in inhibiting tumor growth. (C) 2013 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV Multiple FAS1 domains and the RGD motif of TGFBI act cooperatively to bind alpha v beta 3 integrin, leading to anti-angiogenic and anti-tumor effects Article 10.1016/j.bbamcr.2013.06.012 1 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v.1833, no.10, pp.2378 - 2388 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1833 10 2378 2388 N scie scopus 000322859300026 2-s2.0-84880266999 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article GROWTH-FACTOR-BETA ALPHA(V)BETA(3) INTEGRIN CELL-ADHESION TUMORIGENIC PHENOTYPE TUMOR ANGIOGENESIS BETAIG-H3 GENE CANCER-CELLS IN-VITRO BETA-IG-H3 PROTEIN TGFBI Angiogenesis alpha v beta 3 integrin Anti-tumor effect FAS1 domain