CD 146 positive bone marrow mesenchymal stem cells in advanced stages of untreated lung and breast cancer patients

FERNANDEZ VALLONE, V.; CHOI, H.; LAVOBSKY, V.; MARTINEZ, L.; BORDENAVE, R. H.; FELDMAN, L.; CHASSEING, N. A.

Philadelphia

Congreso; Metastasis and the tumor microenvironment; 2010

American Association for Cancer Research

CD 146 positive bone marrow mesenchymal stem cells in advanced stages of untreated lung and breast cancer patients. Fernandez Vallone VB.*1, Choi H.*2, Labovsky V. 1, Martinez L.1, Bordenave R H. 1, Feldman L. 1, Chasseing NA. 1 *Both authors share equal contribution. 1 Institute for Experimental Biology and Medicine, Buenos Aires, Argentina. 2Institute for Regenerative Medicine, Health Science Center College of Medicine, Temple, Texas, USA. Mesenchymal stem cells (MSC) from bone marrow (BM) multipotentiality or plasticity has been defined as the capacity of these cells to give at least three specific lineages from mesenchymal origin: osteocyte, chondrocyte and adipocyte. It have been described that MSC with higher self-renewal (> CFU-F size = > number of stromal cells/CFU-F) are those that have higher plasticity and migration capacity. In non-treated advanced breast cancer and lung cancer patients without BM and bone metastasis (BCP and LCP), we have found that BM reserve of MSC have a significantly lower differentiation capacity not only in the osteogenic but also in the adipogenic lineage at the expense of chondrogenic one, respect to healthy volunteers (HV) values. These data is related with patients` MSC from BM that have deficient cloning efficiency, lower size of CFU-F and release lower levels of Dkk-1 and SDF-1 in conditioned medium from CFU-F cultures (1 CFU-F = 1 MSC) in reference to HV, as well as deficient capacity for regulating hematopoiesis. Other authors indicated that the major expression of CD146 antigen/MSC was found in MSC that present the triple plasticity and higher self-renewal, as well as higher capacity in regulating hematopoiesis in compare with those that express lower CD146/MSC, the last ones belong to unipotential MSC with low cloning efficiency. All these observations led us to evaluate the % of MSC that express CD146 antigen (positive in MSC from the BM vascular niche) as well as the level of expression/MSC in samples from HV, BCP and LCP (untreated advanced patients without BM and bone metastasis). Methodology: Characterization of MSC from vascular niche (CD146) was performed over MSC from low density cultures (100cells/cm2, high % of MSC) from BM of BCP and LCP as well as HV, by flow cytometry. MSC study was performed using 29 surface markers in double combinations: CD34-, CD36-, CD19-, CD11b-, CD45-, CD184-, CD3-, CD79a-, CD117-, CD271-, CD14-, HLAII-, cMet-, CD49bhigh,CD106low, CD49d+, CD166+, PODXL+, CD90+, CD105+, CD49c+, CD147+, CD29+, CD146+, CD59+, HLAa,b,c+, CD49f+, CD73+, CD44+).  Results: BCP and LCP presented lower % of MSC population with CD146+, as well as a decrease in the relative fluorescence index of CD146, in compare with HV. Conclusion: the results show that these untreated advanced BCP and LCP presented a lower number of MSC from vascular niche before bone metastasis. Therefore, these results in relation with the previous one obtained by our group help us to conclude that these patients have lower reserve in BM of those MSC with high self-renewal, survival, migration and multipotential capacity. These may be explained by the fact that probably at the beginning of the tumor development the most effective MSC have migrated to primary tumor as it have been described in murine models.