Stromal Cell Derived factor-1: Its Influence on Invasiveness and Migration of Breast Cancer Cells in Vitro, and Its Association With Prognosis and Survival in Human Breast Cancer

Breast Cancer Res. 2005;7(4):R402-10. doi: 10.1186/bcr1022. Epub 2005 Apr 4.

Abstract

Introduction: Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer.

Method: Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120).

Results: SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1+/+) or with control plasmid pcDNA4/GFP (MDA-MB-231+/-). MDA-MB-231SDF1+/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231+/-; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and incidence-free survival (P = 0.035).

Conclusion: SDF-1 can increase the invasiveness and migration of breast cancer cells. Its levels correlated with node involvement and long-term survival in patients with breast cancer. SDF-1 may therefore have potential value in assessing clinical outcomes of patients with breast cancer.

MeSH terms

  • Breast / cytology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Movement*
  • Chemokine CXCL12
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / genetics
  • Chemokines, CXC / physiology*
  • Female
  • Fibroblasts
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Neoplasm Invasiveness / physiopathology*
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC