Zhang Chentian, Shenk Elizabeth M, Blaha Laura C, Ryu Byungwoo, Alani Rhoda M, Cabodi Mario, Wong Joyce Y
Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
Biofabrication. 2015 Dec 30;8(1):015001. doi: 10.1088/1758-5090/8/1/015001.
How metastatic cancer lesions survive and grow in secondary locations is not fully understood. There is a growing appreciation for the importance of tumor components, i.e. microenvironmental cells, in this process. Here, we used a simple microfabricated dual cell culture platform with a 500 μm gap to assess interactions between two different metastatic melanoma cell lines (1205Lu isolated from a lung lesion established through a mouse xenograft; and WM852 derived from a stage III metastatic lesion of skin) and microenvironmental cells derived from either skin (fibroblasts), lung (epithelial cells) or liver (hepatocytes). We observed differential bi-directional migration between microenvironmental cells and melanoma, depending on the melanoma cell line. Lung epithelial cells and skin fibroblasts, but not hepatocytes, stimulated higher 1205Lu migration than without microenvironmental cells; in the opposite direction, 1205Lu cells induced hepatocytes to migrate, but had no effect on skin fibroblasts and slightly inhibited lung epithelial cells. In contrast, none of the microenvironments had a significant effect on WM852; in this case, skin fibroblasts and hepatocytes--but not lung epithelial cells--exhibited directed migration toward WM852. These observations reveal significant effects a given microenvironmental cell line has on the two different melanoma lines, as well as how melanoma effects different microenvironmental cell lines. Our simple platform thus has potential to provide complex insights into different strategies used by cancerous cells to survive in and colonize metastatic sites.
转移性癌灶如何在继发部位存活和生长尚未完全明确。人们越来越认识到肿瘤成分，即微环境细胞，在这一过程中的重要性。在此，我们使用了一种简单的微加工双细胞培养平台，其间隙为500μm，以评估两种不同的转移性黑色素瘤细胞系（1205Lu，从通过小鼠异种移植建立的肺部病变中分离得到；WM852，源自皮肤III期转移性病变）与来自皮肤（成纤维细胞）、肺（上皮细胞）或肝（肝细胞）的微环境细胞之间的相互作用。我们观察到微环境细胞与黑色素瘤之间存在不同的双向迁移，这取决于黑色素瘤细胞系。肺上皮细胞和皮肤成纤维细胞，而非肝细胞，刺激1205Lu的迁移比没有微环境细胞时更高；在相反方向上，1205Lu细胞诱导肝细胞迁移，但对皮肤成纤维细胞没有影响，对肺上皮细胞有轻微抑制作用。相比之下，没有一种微环境对WM852有显著影响；在这种情况下，皮肤成纤维细胞和肝细胞——而非肺上皮细胞——表现出向WM852的定向迁移。这些观察结果揭示了特定的微环境细胞系对两种不同黑色素瘤细胞系的显著影响，以及黑色素瘤如何影响不同的微环境细胞系。因此，我们的简单平台有可能为癌细胞在转移部位存活和定植所采用的不同策略提供复杂的见解。
