Bone marrow reserve of MSC in untreated advanced breast cancer patients: a reservoir of the disease.

FERNANDEZ VALLONE VB; CHOI H; MARTINEZ L; BORDENAVE R H; BATAGELJ E, ; FELDMAN L, ; LABOVSKY V, ; CHASSEING NA

Orlando

Congreso; Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy, Special Conference; 2011

AACR

We found that bone marrow (BM) mesenchymal stem cells (MSC) from untreated advanced breast cancer patients, before bone metastasis (BCP), have lower osteogenic differentiation compared to healthy volunteers (HV). Data related with the deficient cloning efficiency of BCP-MSC, and lower levels of Dkk1 and SDF1 released by MSC in reference to HV. Also, BCP presented lower number of MSC from vascular niche. So we propose that BCP have lower reserve in BM of those MSC with high self-renewal and plasticity. Some authors have described that the more cloning efficiency of MSC the more migration capacity and that migration could be antagonized by MIF. For all this, MIF was quantified by ELISA in peripheral blood (PB) plasma from 7BCP and 9HV. Also expression of alpha2beta1 and VCAM-1 in BM-MSC from BCP and HV were analyzed by FAC. MIF levels were higher in BCP than HV (p=0.005). The % BCP-MSC with alpha2beta1 positive was significantly higher than HV (53+/-14 and 5+/-61), meanwhile the % of BCP-MSC with VCAM-1 positive expression was significantly lower than in HV (14+/-9 and 46+/-8). So MIF higher levels in BCP are consistent with the idea that MSC remaining in BCP-BM cannot migrate outside and that those that have already gone to the primary tumor or other metastatic sites remain there after homing. Higher expression of alpha2beta1 may keep these MSC, with lower cloning efficiency and plasticity, by their interaction with laminin and collagen. Moreover, lower VCAM-1 expression may be related with less interaction with hematopoietic and endothelial progenitors through VLA-4.