Abstract: VCAM-1 (CD106), a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1). In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT) program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGFβ1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.
Keywords: VCAM-1; breast cancer progression; EMT; metastasis; chemoresistance
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Wang, P.-C.; Weng, C.-C.; Hou, Y.-S.; Jian, S.-F.; Fang, K.-T.; Hou, M.-F.; Cheng, K.-H. Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells. Int. J. Mol. Sci. 2014, 15, 3560-3579.
Wang P-C, Weng C-C, Hou Y-S, Jian S-F, Fang K-T, Hou M-F, Cheng K-H. Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells. International Journal of Molecular Sciences. 2014; 15(3):3560-3579.
Wang, Pei-Chen; Weng, Ching-Chieh; Hou, You-Syuan; Jian, Shu-Fang; Fang, Kuan-Te; Hou, Ming-Feng; Cheng, Kuang-Hung. 2014. "Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells." Int. J. Mol. Sci. 15, no. 3: 3560-3579.