Vartanian Amalia, Karshieva Saida, Dombrovsky Vladislav, Belyavsky Alexander
Department of Experimental Diagnosis and Biotherapy of Tumors, Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
Laboratory of Stem and Progenitor Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Oncol Lett. 2016 Jun;11(6):4264-4268. doi: 10.3892/ol.2016.4523. Epub 2016 May 5.
Accumulating evidence suggests that mesenchymal stromal cells (MSCs) are recruited to the tumor, and promote tumor development and growth. The present study was performed to investigate the communication between aggressive melanoma and MSCs in vasculogenic mimicry (VM). Normal human MSCs plated on Matrigel were unable to form capillary-like structures (CLSs). By contrast, MSCs co-cultured with aggressive melanoma cell lines, namely, Mel Cher, Mel Kor and Mel P, generated CLSs. Significantly, MSCs co-cultured with poorly aggressive melanoma cells, namely, Mel Me, failed to form CLSs. To identify factors responsible for VM, the effects of vascular endothelial growth factor A (VEGFA), pro-epidermal growth factor, basic fibroblast growth factor and stromal cell-derived factor 1α on the formation of CLSs by MSCs were tested. VM was induced by the addition of VEGFA, whereas other cytokines were inefficient. To confirm the hypothesis that aggressive tumor cells can increase the vasculogenic ability of MSCs, a standard B16/F10 mouse melanoma test system was used. MSCs isolated from the adipose tissues of C57BL/6 mice with melanoma formed a vascular-like network on Matrigel, whereas MSCs from healthy mice failed to form such structures. This study provides the first direct evidence that melanoma tumors educate MSCs to engage in VM. The education may occur distantly. These findings offer promise for novel therapeutic directions in the treatment of metastatic melanoma.
越来越多的证据表明，间充质基质细胞（MSC）被募集到肿瘤中，并促进肿瘤的发展和生长。本研究旨在探讨侵袭性黑色素瘤与MSC在血管生成拟态（VM）中的相互作用。接种在基质胶上的正常人MSC无法形成毛细血管样结构（CLS）。相比之下，与侵袭性黑色素瘤细胞系（即Mel Cher、Mel Kor和Mel P）共培养的MSC能够形成CLS。值得注意的是，与低侵袭性黑色素瘤细胞（即Mel Me）共培养的MSC未能形成CLS。为了确定参与VM的因素，测试了血管内皮生长因子A（VEGFA）、前表皮生长因子、碱性成纤维细胞生长因子和基质细胞衍生因子1α对MSC形成CLS的影响。添加VEGFA可诱导VM，而其他细胞因子则无效。为了证实侵袭性肿瘤细胞可增强MSC血管生成能力这一假说，使用了标准的B16/F10小鼠黑色素瘤测试系统。从患有黑色素瘤的C57BL/6小鼠脂肪组织中分离出的MSC在基质胶上形成了血管样网络，而来自健康小鼠的MSC则未能形成此类结构。本研究提供了首个直接证据，表明黑色素瘤肿瘤可促使MSC参与VM。这种作用可能在远处发生。这些发现为转移性黑色素瘤的治疗提供了新的治疗方向。
