Abstract
VCAM-1 (CD106) is a transmembrane glycoprotein that is involved in many pathological inflammatory processes. VCAM-1 plays an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1). In our preliminary data, we first identified that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation and directly correlated with breast tumor progression; however, its mechanism of action in tumor biology remains unknown. Here, we describe the establishment and use of breast cancer cell line model systems to dissect the functional roles of VCAM-1 activation in the manifestation of malignant phenotypes of human breast cancer. We show that VCAM-1 overexpression in the NMuMG breast epithelial cells increase cell adhesion and motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in an established metastatic breast cancer cell line, MDAMB231, we confirmed that the knockdown of endogenous VCAM-1 expression by small interfering RNA (SiRNA) reduced cell proliferation and inhibited TGFb1 or IL6 mediated cell migration. Furthermore, we also demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced the tumor formation in an SCID xenograft mouse model. In conclusion, our findings uncover the critical role of VCAM-1 activation in facilitating breast cancer progression by enhancing the malignant properties of breast cancer cells and suggest that targeting of VCAM-1 induced pathways is an attractive strategy for therapeutic intervention.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B60.
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