How bone marrow microenvironment prepares the bone pre-metastatic niche for breast cancer cells?

MARTINEZ LM; FERNANDEZ VALLONE, VB; LABOVSKY, V.; CHOI H; HOFER EL; FELDMAN, L; BORDENAVE, RH; BATGELJ, E; DIMASE, F; RODRIGUEZ VILLAFAÑE A; CHASSEING, NA

Miami

Conferencia; 13th International Conference on Cancer-Induced Bone Disease (CIBD) - International Bone and Mineral Society (IBMS); 2013

International Bone and Mineral Society (IBMS).

Abstract Bone metastasis is an incurable complication of breast cancer (BC) affecting approximately 70% of advanced patients. Although novel findings demonstrate the bone marrow (BM)-microenvironment significance in BC progression, the majority of studies have focused on end-stage disease, but little is known about the how is the BM preparing the bone pre-metastatic niche. In this study, we demonstrated that BC induces substantial changes in peripheral blood (PB) and BM-microenvironments of untreated advanced patients without bone metastasis compared with healthy volunteers (HV). Data suggest that high RANKL, MIF and OPG levels in BC patient (BCP)-PB could play a role in the intravasation, angiogenesis, survival and epithelial-to-mesenchymal transition (EMT) phenotypes of circulating BC cells (BCCs). Interestingly, ICAM-1, VCAM-1 and PDGF-AB levels in BCP-BM plasma were significantly higher than HV-values, suggesting that they could be involved in the BCC escape from the blood vessels into the BM. We demonstrated that BCP-BM-mesenchymal stem cells could control the recruitment of the BCCs modifying the MCF-7 and MDA-MB231 cell migration. In addition to its angiogenic and EMT properties, PDGF-AB could be responsible for the higher proliferation of MDA-MB231 cells when we used BCP-BM plasma compared with HV-plasma. Finally, the high PDGF-AB, ICAM-1 and VCAM-1 levels in the BM plasma would increase bone resorption, leading to BCC invasion and proliferation. Taken together, the BM of untreated advanced BCP without bone metastasis provides an ideal environment for the development of the pre-metastatic niche.