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Mentions: SDF-1 mRNA was identified in MRC5, MDA-MB-435s, MDA-MB-436 and breast cancer tissues, but not in other breast cancer cell lines and HECV cells. It has been suggested that the MDA-MB-435 cell line is of melanocyte origin, and MDA-MB-436 was the only SDF-1 positive breast cancer cell line of all the lines tested in the present study. In contrast, CXCR4 mRNA expression was detected in all eight breast cancer cell lines, in MRC5 and HECV cells (Fig. 1), and in breast cancer tissue (data not shown). Quantitative analysis of the SDF-1 transcript revealed that breast tumour tissues had high levels of SDF-1 transcript (mean ± standard deviation: 195 ± 103 copies) as compared with normal mammary tissues (85.6 ± 54), but the difference was not statistically significant (P = 0.35). To take into account the contribution made by cellularity in mammary tissues, levels of SDF1 were normalized to the level of CK19. Dispite a higher SDF1:CK19 ratio in tumour tissues (39.3 ± 13.6) than in normal breast tissue (30.7 ± 3.97), the difference was not significant (P = 0.84). With respect to ER, those tumours negative for ER had higher levels of SDF-1 (246 ± 138) than did ER-positive tumours (57.9 ± 45.4; P = 0.20). A similar, insignificant trend was seen with ER-β (248.0 ± 131 for ER-β- tumours and 1.3 ± 0.72 for ER-β+ tumours). The SDF-1:CK19 ratio for ER-negative tumours was 52.7 ± 41.6 and that for ER-positive tumours was 30.8 ± 14.4 (P = 0.62). The ratio was 41.2 ± 17.3 for ER-β-negative and 8.3 ± 5.1 for ER-β-positive tumours (P = 0.072).
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
Bottom Line: 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).It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and incidence-free survival (P = 0.035).SDF-1 may therefore have potential value in assessing clinical outcomes of patients with breast cancer.
Affiliation: Wales College of Medicine, Cardiff University, Cardiff, UK.
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.
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