TY - JOUR
T1 - Stable Changes in Mesenchymal Stromal Cells from Multiple Myeloma Patients Revealed through Their Responses to Toll-Like Receptor Ligands and Epidermal Growth Factor
AU - Pevsner-Fischer, Meirav
AU - Levin, Sarit
AU - Hammer-Topaz, Tal
AU - Cohen, Yifat
AU - Mor, Felix
AU - Wagemaker, Gerard
AU - Nagler, Arnon
AU - Cohen, Irun Robert
AU - Zipori, Dov
N1 - Funding Information:
Acknowledgements This study was supported by the Helen and Martin Kimmel Institute for Stem Cell Research and the M.D. Moross Institute for Cancer Research, at the Weizmann Institute, the Charles and David Wolfson Charitable Trust, grant No. 2003117 from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel and by grants from the Gabrielle Rich Center for Transplantation Biology. We gratefully acknowledge support for this project provided by a grant from the Legacy Heritage Fund of New York.
PY - 2012/6
Y1 - 2012/6
N2 - In human multiple myeloma (MM), the tumor cells exhibit strict dependence on bone marrow (BM) stromal elements. It has been suggested that, in turn, MM cells modify multipotent stromal cells (MSCs), diverting them to support the myeloma. We investigated MM-derived MSCs by comparing their toll-like receptor (TLR) responses to those of MSCs derived from healthy controls. We now report that MM-derived MSCs manifested intact proliferation responses and IL-6 secretion and their adipose and osteogenic differentiation responses to TLR ligands were also similar to those of healthy controls, ranging from augmentation to inhibition. However, MM-derived MSCs were found to be defective in IL-8 secretion and ERK1/2 phosphorylation following TLR-2 activation. Moreover, MM-derived MSCs failed to respond to EGF by elevation of ERK1/2 phosphorylation. The persistence of these changes in extensively cultured MM-derived MSCs, suggests that these cells are stably, if not irreversibly modified.
AB - In human multiple myeloma (MM), the tumor cells exhibit strict dependence on bone marrow (BM) stromal elements. It has been suggested that, in turn, MM cells modify multipotent stromal cells (MSCs), diverting them to support the myeloma. We investigated MM-derived MSCs by comparing their toll-like receptor (TLR) responses to those of MSCs derived from healthy controls. We now report that MM-derived MSCs manifested intact proliferation responses and IL-6 secretion and their adipose and osteogenic differentiation responses to TLR ligands were also similar to those of healthy controls, ranging from augmentation to inhibition. However, MM-derived MSCs were found to be defective in IL-8 secretion and ERK1/2 phosphorylation following TLR-2 activation. Moreover, MM-derived MSCs failed to respond to EGF by elevation of ERK1/2 phosphorylation. The persistence of these changes in extensively cultured MM-derived MSCs, suggests that these cells are stably, if not irreversibly modified.
KW - ERK phosphorylation
KW - Epidermal growth factor, EGF
KW - Multiple myeloma
KW - Multipotent stromal cells, MSCs
KW - Toll-like receptors, TLR
UR - http://www.scopus.com/inward/record.url?scp=84861702173&partnerID=8YFLogxK
U2 - 10.1007/s12015-011-9310-2
DO - 10.1007/s12015-011-9310-2
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C2 - 21881833
AN - SCOPUS:84861702173
SN - 2629-3269
VL - 8
SP - 343
EP - 354
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 2
ER -
