Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Clin Cancer Res. 2012 Jan 15;18(2):342-9. doi: 10.1158/1078-0432.CCR-11-2212. Epub 2011 Nov 7.
Hematologic malignancies rely heavily on support from host cells through a number of well-documented mechanisms. Host cells, specifically mesenchymal stem cells (MSC), support tumor cell growth, metastasis, survival, bone marrow colonization, and evasion of the immune system. In multiple myeloma, similar to solid tumors, supporting cells have typically been considered healthy host cells. However, recent evidence reveals that many MSCs derived from patients with multiple myeloma (MM-MSC) show significant defects compared with MSCs from nondiseased donors (ND-MSC). These abnormalities range from differences in gene and protein expression to allelic abnormalities and can initiate after less than 1 day of coculture with myeloma cells or persist for months, perhaps years, after removal from myeloma influence. Alterations in MM-MSC function contribute to disease progression and provide new therapeutic targets. However, before the scientific community can capitalize on the distinctions between MM-MSCs and ND-MSCs, a number of confusions must be clarified, as we have done in this review, including the origin(s) of MM-MSCs, identification and characterization of MM-MSCs, and downstream effects and feedback circuits that support cancer progression. Further advances require more genetic analysis of MM-MSCs and disease models that accurately represent MSC-MM cell interactions.
血液系统恶性肿瘤严重依赖宿主细胞通过多种有充分文献记载的机制提供支持。宿主细胞，特别是间充质干细胞（MSC），支持肿瘤细胞的生长、转移、存活、骨髓定植和逃避免疫系统。在多发性骨髓瘤中，与实体瘤类似，支持细胞通常被认为是健康的宿主细胞。然而，最近的证据表明，许多源自多发性骨髓瘤患者的间充质干细胞（MM-MSC）与来自非疾病供体的间充质干细胞（ND-MSC）相比表现出明显的缺陷。这些异常范围从基因和蛋白表达的差异到等位基因异常，并且可以在与骨髓瘤细胞共培养不到 1 天后发生，或者在从骨髓瘤影响中去除后持续数月甚至数年。MM-MSC 功能的改变导致疾病进展，并提供了新的治疗靶点。然而，在科学界能够利用 MM-MSC 和 ND-MSC 之间的区别之前，必须澄清许多混淆，就像我们在这篇综述中所做的那样，包括 MM-MSC 的起源、MM-MSC 的鉴定和表征，以及支持癌症进展的下游效应和反馈回路。进一步的进展需要对 MM-MSC 进行更多的遗传分析，并需要更准确地代表 MSC-MM 细胞相互作用的疾病模型。
