CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo

Int J Clin Exp Pathol. 2014 Sep 15;7(10):6671-8. eCollection 2014.

Abstract

Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of CXCL12 and relevance with clinicopathological factors in the invasive ductal carcinoma. Reduction of CXCL12 was significantly correlated with tumor size, lymph node metastasis, TNM stage and Her-2 expression in breast cancer. Patients with negative CXCL12 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive CXCL12 expression. In addition, we demonstrated that upregulation of CXCL12 expression by infection with an adenovirus containing a CXCL12 vector significantly inhibited cell growth and reduced the migration of breast cancer cells. Furthermore, animal studies revealed that nude mice injected with the Ad-CXCL12 cell lines featured a lighter weight than the control cell lines. These data suggest that CXCL12 plays an important role in cell growth and invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.

Keywords: Breast carcinoma; CXCL12; growth; metastasis; nude mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / immunology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary
  • Cell Proliferation*
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12