Expression of osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, tumor necrosis factor-related apoptosis-inducing ligand, stromal cell-derived factor-1 and their receptors in epithelial metastatic breast cancer cell lines.

LABOVSKY VIVIAN ; FERNÁNDEZ VALLONE VB; MARTINEZ LM; OTAEGUI J; CHASSEING NA

CANCER CELL INTERNATIONAL

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2012 vol. 12 p. 29 - 41

1475-2867

Background: Breast cancer (BC) remains the major cause of death among women worldwide. Despite efforts to detect BC in early stages, there is no guarantee of better patients’ survival because many of them develop primarily metastases. Bone metastasis is a common complication of BC and occurs in 65-80% of patients with metastatic BC. The complexities of the metastatic process have yet to be fully elucidated, and few therapeutic or preventive strategies successfully target this stage of carcinogenesis. The molecules underlying metastatic “dormancy”, as well as dissemination and metastatic establishment, remain enigmatic. Based on these observations, the objective of the present study was to evaluate simultaneously osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), tumor necrosis factor related apoptosis inducing ligand (TRAIL), stromal cell-derived factor-1 (SDF-1), and their receptors (R) in two human BC cell lines like MDA-MB231 (high invasive and metastatic cells, independient-estrogen), and MCF-7 (low invasive and metastatic cells, dependent-estrogen). Methods: OPG, RANKL, TRAIL and SDF-1 expression and release, as well as the expression of their receptors were evaluated by immunofluorescence, immunocytochemistry, western blot and ELISA assays. Results: We have shown that MCF-7 released higher levels of OPG in the conditioned media (CM) than MDA-MB231 and 100% of the cells of both lines expressed OPG, RANKL, TRAIL and SDF-1. Moreover, 100% of the cells from both lines expressed membrane RANKL and RANK, meanwhile 50% of them expressed CX-CR4. Finally, 100% of the cells in both lines expressed TRAIL-R1 and R4, 30-50% TRAIL-R2, and 40-55% TRAIL-R3. Conclusion: We concluded that cells from MCF-7 and MDA-MB231 only released OPG but expressed RANKL, TRAIL and SDF-1. Also, the major of these cell lines expressed RANK, CXCR4 and TRAIL-R. Therefore, as ligands and receptors evaluated are implicated in the regulation of the proliferation, survival, migration and future bone metastasis during breast tumor-progression, the study of these molecules in tumor-biopsies of BC patients could be useful to identify those patients with more aggressive tumors as well as bone risk, and thus may improve the choices for therapy.