IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CD 146 positive bone marrow mesenchymal stem cells in advanced stages of untreated lung and breast cancer patients
Autor/es:
FERNANDEZ VALLONE, V.; CHOI, H.; LAVOBSKY, V.; MARTINEZ, L.; BORDENAVE, R. H.; FELDMAN, L.; CHASSEING, N. A.
Lugar:
Philadelphia
Reunión:
Congreso; Metastasis and the tumor microenvironment; 2010
Institución organizadora:
American Association for Cancer Research
Resumen:
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.