Association between of ligands and receptors related to the progression of early breast cancer in tumor epithelial and stromal cells

LABOVSKY V; MARTINEZ LM; DAVIES KM; GARCÍA-RIVELLO H; CALCAGNO ML; MATAS A; FERNÁNDEZ VALLONE VB; WERNICKE A; CHASSEING NA

Clinical Breast Cancer

ELSEVIER

Lugar: Philadelphia; Año: 2015 vol. 15 p. 13 - 21

1526-8209

We demonstrated the association between RANKL, IL-6, SDF-1 and CCL-2 in tumor epithelial cells and their receptors in spindle shaped stromal cells, as well as, between TRAIL, RANKL and CCL2 in spindle shaped stromal cells and their receptors in tumor epithelial cells from 63 breast cancer patients (I/II-stage). These molecules could be implicated in the breast cancer progression during early stage of the disease. Introduction: Despite advances in its study, breast cancer (BC) remains the second leading cause of mortality among women. BC is a heterogeneous cellular milieu comprised of tumor and stromal cells (SC). Their interaction plays a major role in BC progression. It is mainly driven by soluble secreted factors and has been described as a two-way street due to the ability of tumor epithelial cells (TEpC) to influence the stroma and vice versa. The aim of the present study was to evaluate the association between ligands and receptors (R) expression (OPG, TRAIL, RANKL, SDF-1, IL-6,MCSF,CCL-2 and their R) in TEpC and spindle shaped SC not closely associated with the vasculature. Patients and Methods: We examined these factors´ expression in 63 primary tumors of untreated-BC patients (BCP) with infiltrative ductal carcinoma (I/II stage) and 10 non-neoplastic tissues. The percentage of positive cells and the staining intensity was analyzed by immunohistochemistry. Mann-Whitney test and Spearman´s rank correlation coefficient were used (p=0.05). Results: We found a significant association between the expression of RANKL, IL-6, SDF-1 and CCL-2 in TEpC with the RANK, IL-6R, CXCR-4 and CCR-2 in spindle shaped SC. Moreover, significant association was found between the expression of TRAIL, RANKL and CCL-2 in spindle shape SC with the expression of TRAIL-R1, TRAIL-R4, RANK, and CCR-2 in TEpC. Discussion: Since these ligands and R are implicated in BC progression, our results suggest that these factors could be involved in the crosstalk between TEpC and SC in the early steps of BC stage.