Stable Changes in Mesenchymal Stromal Cells from Multiple Myeloma Patients Revealed through Their Responses to Toll-Like Receptor Ligands and Epidermal Growth Factor

M Pevsner-Fischer, S Levin, T Hammer-Topaz, Y Cohen, F Mor, Gerard Wagemaker, A Nagler, IR Cohen, D Zipori

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)343-354
Number of pages12
JournalStem Cell Reviews
Volume8
Issue number2
DOIs
Publication statusPublished - 2012

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