Endothelial Cell VE-cadherin Functions as a Receptor for the β15–42 Sequence of Fibrin

The VE‐cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells

“…2,14,[32][33][34][35][36][37] In addition, others have demonstrated Fg production in adenocarcinoma cell lines of cervical 15 and intestinal 16 origin. Recent expression array profiling studies have confirmed that the Fg genes are expressed in breast 17 and lung carcinomas 18,19 isolated from patients. Thus, cancer cell-specific synthesis of Fg promotes growth of the primary tumor and further supports tumorassociated angiogenesis, 38 which is characterized by localized vascular permeability factor, i.e., VEGF production and leaky vessels.…”

“…Both MoAbs T2G1 (anti-FgBb [15][16][17][18][19][20][21] ) and BV9 (anti-VE-cadherin EC3-EC4), but not MoAb 18C6 (anti-FPB Bb [1][2][3][4][5][6][7][8][9][10][11][12][13][14], partially inhibited Fg-induced FITCDextran Flux, implicating VE-cadherin and Fg-b in mechanisms of Fg-induced EC permeability. Fg is capable of inducing permeability of different types of barrier EC, as Fg also induced permeability of a microvascular EC barrier, whereas it did not induce permeability of an epithelial cell barrier.…”

“…The negative control peptide corresponding to fibrinopeptide A induced minimal %FITC-Dextran Flux compared with Fg or peptide b 15-42 (#p < 0.0001); however, the 13% relative fluorescence was significant (-p 5 0.001) compared with basal levels that were 1% of intact Fg-induced permeability. Peptides missing b 15-17 residues (b [18][19][20][21][22][23][24][25][26][27][28][29][30][31] or b [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] ) or truncated at the C-terminus (b [15][16][17][18][19][20][21][22][23][24][25][26][27] (Fig. 2c).…”

“…14,[26][27][28] Control experiments indicated that Fg added to breast cancer or endothelial cells was not processed further by protease degradation or crosslinking to higher ordered structures (data not shown). Synthetic peptides corresponding to the Fg b-chain primary structure were custom synthesized as previously described, 11 and include b , b [15][16][17][18][19][20][21][22][23][24][25][26][27] , b 18-31 and b [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] (Table I). Fibrinopeptide A (Bachem) was used as a nonspecific peptide for permeability studies.…”

“…VE-cadherin also supports EC capillary tube formation in fibrin gels, 15 which requires exposure of the fibrin b 15-42 neo-aminoterminus 16 ; portions of the third and fourth extracellular domains of VE-cadherin constitute a fibrin b 15-42 receptor. 17,18 Using the fibrin-specific monoclonal antibody (MoAb) T2G1, we showed that binding of fibrin monomer to the surface of EC is b 15-42 -dependent, which leads to reduced accessibility of b 15-21 to T2G1. 11 In addition, the b 15-42 region of matrix-Fg is required for accelerated wound closure in a response-to-injury model of wound healing.…”