Abstract
BackgroundThe interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites.MethodsHere we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases.ResultsWe show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion.ConclusionWe conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1556-7) contains supplementary material, which is available to authorized users.
Highlights
The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors
Breast cancer cells interact with bone marrow host cells (BMHC) Tumor stroma is a composed of multiple cell types; we have previously described [33] the infiltration of ovarian cancer tumors by Bone Marrow host cells (BMHCs) (CD9+CD10+)
When the two cell types were seeded at the same time at a ratio of 1/1, breast cancer cells (BCC) attached preferentially on BMHC compare to plastic or matrigel as shown on phase contrast and selected (x-z) sections, obtained from confocal microscopy (Fig. 1c-d)
Summary
The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites. Among chemokines implicated in this cascade; SDF-1α/CXCR4 regulates organ specific colonization of metastatic tumor cells [3,4,5,6]. CXCR4 is over-expressed in many breast cancer cells (BCC), promoting cancer cell migration and invasion [8]. BCC differential chemokine receptor expression is correlated with their metastatic behavior [9].
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