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. 2010 Sep;1(5):845-847.
doi: 10.3892/ol_00000149. Epub 2010 Sep 1.

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

Brian A Zabel  1 , Zhenhua Miao, Nu L Lai, Yu Wang, Susanna Lewén, Robert D Berahovich, Juan C Jaén, Thomas J Schall
Affiliations

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

Brian A Zabel et al. Oncol Lett. 2010 Sep.

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.

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Figures

Figure 1
Figure 1
hMMP-3 is selectively upregulated in MDA-MB-435s human breast cancer cells that overexpress CXCR7. The fold increase in analyte concentrations in conditioned media from 435-CXCR7 cells over 435-WT cells is shown. n=2 samples per cell type per culture condition.
Figure 2
Figure 2
The 435-CXCR7 xenografts express hMMP-3 in vivo. A total of 1 million 435-WT, 435-empty vector control or 435-CXCR7 cells were implanted subcutaneously into SCID mice on day 0. On the indicated days post-implantation, serum was collected and analyzed for hMMP-3 levels using ELISA. Each closed circle represents an individual mouse, and the mean for each group is shown. *p<0.05, Mann-Whitney rank sum test. †The Q-test was used to eliminate the indicated outlier (confidence limit >99%). Representative of two independent experiments.
Figure 3
Figure 3
CXCR7 RNAi-knockdown downregulates mMMP-3 in 4T1 mouse mammary cancer cells. A total of 1 million 4T1-WT or 4T1-CXCR7-RNAi-985 cells were cultured in vitro for the indicated times. mMMP-3 levels in the conditioned media were determined by ELISA. The mean ± SEM is shown for triplicate wells. *p<0.05, Student's t-test.
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References

    1. Morris PG, McArthur HL, Hudis CA. Therapeutic options for metastatic breast cancer. Expert Opin Pharmacother. 2009;10:967–981. - PubMed
    1. Brunello A, Roma A, Falci C, Basso U. Chemotherapy and targeted agents for elderly women with advanced breast cancer. Recent Pat Anticancer Drug Discov. 2008;3:187–201. - PubMed
    1. Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1–22. - PubMed
    1. Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R, Abbruzzese JL. Metastatic patterns in adenocarcinoma. Cancer. 2006;106:1624–1633. - PubMed
    1. Zlotnik A. Involvement of chemokine receptors in organ-specific metastasis. Contrib Microbiol. 2006;13:191–199. - PubMed

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