Evaluation of SDF-1/CXCR4 expression in human HER2/NEU positive breast cancer samples

Abstract

Stromal Derived Factor-1 (SDF-1) is a chemokine whose membrane receptor CXCR4 can be found in breast tumor and the metastatic sites of the primary tumor. The signaling pathway of this chemokine and its receptor is involved and is capable to induce directional migration of cells due to a chemokine gradient. Recently, it has been observed that CXCR4 works as a mediator in the migration of tumor cells to specific organs and t it could be correlated with expression of the Human Epidermal )rowth Factor Receptor-2 (HER2/neu) in breast tumors. HER2/neu is a transmembrane protein, also known as ErbB-2, which has been implicated in many types of human cancers, specifically breast cancer, in which it is used as a prognostic factor. We hypothesized that the overexpression of HER2/neu activates the SDF-1/CXCR4 axis in HER2/neu positive breast tumors, and that transactivation enhances tumor progression, malignancy and metastasis capacity. The aim of this work was to investigate the association between SDF-1/CXCR4 and HER2/neu expression in breast cancer paraf- fin sections. We carried out an RT-qPCR of human breast tumor paraffin samples to determine the SDF-1 and CXCR4 expression. We, additionally, performed the same SDF-1/CXCR4 RT-qPCR in some of the metastatic sites of the primary tumor. Also, analysis of HER2/neu expression in these samples were determined by immunohistochemistry. Most HER2/neu positive breast tumor paraffin samples were found to express high levels of either SDF-1 of CXCR4. Some of the metastatic sites presented higher levels of this chemokine and its receptor expression, while others presented no expression at all. Further investigation is needed, particularly in HER2/neu negative samples, in order to achieve acceptable information to validate our hypothesis.