Breast cancer cell and bone marrow microenvironment: The seed and soil

MARTINEZ LM; FERNÁNDEZ VALLONE VB; CHOI H; LABOVSKY V; BORDENAVE RH; BATAGELJ E; FELDMAN L; DIMASE F; CHASSEING NA

Dalian

Congreso; BIT 6th Annual World Congress of Molecular & Cell Biology; 2016

BIT Congress Inc

Bone metastasis is an incurable complication of advanced breast cancer patients (BCP). It is a multistep process that includes tumor cell extravasation, migration and proliferation in bone marrow (BM)/bone. Although novel findings demonstrate the BM-microenvironment relevance in the bone metastatic progression, little is known about how the pre-metastatic niche arises in the BM/bone. We demonstrated a significant increase in BCP-BM-plasma capacity to induce both transendothelial migration of MDA-MB231 and MCF-7 cells and proliferation of MDA-MB231 cells compared with healthy volunteers (HV). Interestingly, high PDGF-AB, ICAM-1, VCAM-1 and CCL-2 levels in patients?BM-plasma could be involved in the cancer cell extravasation and proliferation. Furthermore, BCP-conditioned media (CM) from cultures of BM-mesenchymal stem cells (MSC) showed a significant increase of transwell migration of MCF-7 and MDA-MB231 cells compared with control values. This observation was related to the significant higher CCL-2 levels in these BCP-CM. Finally, we observed a significant increase of MMP-9 activity in BCP-CM compared with HV-CM, which could favor the release of embedded growth factors in BM/bone extracellular matrix. So, the study of BM-plasma, as well as, BM-MSC from advanced BCP without bone metastasis may be an approach for early detection of the high risk of bone metastatic occurrence.