CXCR7 protein expression correlates with elevated mmp-3 secretion in breast cancer cells

Abstract

Metastatic breast cancer is the leading cause of cancer-related death in women worldwide and, despite recent therapeutic advances, the disease remains incurable. A critical step in cancer cell metastasis is the degradation of extracellular matrix components by matrix metalloproteinases (MMPs), which permits malignant cells to separate from the primary tumor and access circulatory conduits for seeding distant organs. This study reports a correlation between the elevated secretion of MMP-3 by breast cancer cells and the expression of CCR7 protein, a recently discovered non-classical chemokine receptor that may play a role in metastasis by regulating tumor cell transendothelial migration. MMP-3 secretion is increased in human mammary tumor cells that overexpress CXCR7, and is reduced in mouse breast cancer cells in which the endogenous CXCR7 expression has been knocked down via RNAi. The correlation between CXCR7 and MMP-3 expression in breast cancer may provide additional therapeutic rationale for targeting CXCR7 in order to prevent metastatic disease.