Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Stem Cell Rev Rep. 2012 Jun;8(2):343-54. doi: 10.1007/s12015-011-9310-2.
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.
在人类多发性骨髓瘤（MM）中，肿瘤细胞表现出对骨髓（BM）基质成分的严格依赖性。据推测，反过来，MM 细胞又会改变多能基质细胞（MSCs），促使它们支持骨髓瘤。我们通过比较 MM 衍生的 MSC 与来自健康对照者的 MSC 的 Toll 样受体（TLR）反应，研究了 MM 衍生的 MSC。我们现在报告，MM 衍生的 MSC 表现出完整的增殖反应和 IL-6 分泌，其脂肪和成骨分化反应对 TLR 配体也类似于健康对照者，从增强到抑制。然而，发现 MM 衍生的 MSC 在 TLR-2 激活后 IL-8 分泌和 ERK1/2 磷酸化存在缺陷。此外，MM 衍生的 MSC 未能通过 ERK1/2 磷酸化的升高来响应 EGF。这些变化在广泛培养的 MM 衍生 MSC 中持续存在，表明这些细胞是稳定的，如果不是不可逆的修饰。
