Vink J, Thomas L, Etoh T, Bruijn J A, Mihm M C, Gattoni-Celli S, Byers H R
Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston.
Lab Invest. 1993 Feb;68(2):192-203.
Recent data suggest that the extracellular matrix of organs and heterogeneous integrin expression of tumor cells may influence metastasis distribution.
Three human melanoma cell lines were characterized for integrin expression, in vitro binding to cryostat sections of different organs, and ability to generate experimental metastases in triple immunodeficient mice.
The three cell lines exhibited heterogeneous expression of integrins, binding to cryostat sections, and organ colonization. A primary melanoma cell line (PM-WK) did not give rise to experimental metastases, showed scant or mild attachment to only a few organ tissue sections, and showed absent or minimal expression of alpha-integrin subunits tested (VLA 1-6) and alpha v beta 3. In contrast, two lymph node derived lines exhibited distinct patterns of organ colonization: MM-RU colonized only the lungs and expressed predominantly alpha 2 beta 1 and alpha v beta 3 integrin, whereas MM-AN colonized lung and extrapulmonary sites including pancreas and subcutaneous brown fat and expressed predominantly alpha 2 beta 1 and alpha 6 beta 1 integrin. In vitro, MM-RU exhibited marked attachment to lung, brown fat, kidney, and adrenal with no binding to liver, pancreas, brain, or muscle tissue sections, whereas MM-AN had a similar binding profile but with additional attachment to liver and pancreas. Function blocking anti-beta 1 monoclonal antibody inhibited the attachment of MM-RU and MM-AN cells to these tissues (p < 0.001), whereas function blocking anti-alpha 5 and an unrelated monoclonal antibody (HLA class I) did not. Function blocking anti-alpha 2 monoclonal antibody inhibited MM-RU cell adhesion (p < 0.001) but not MM-AN adhesion. However, the function blocking monoclonal antibody alpha 6 beta 1 significantly inhibited the binding of MM-AN to these tissues.
These data suggest that alpha 2 beta 1 and alpha 6 beta 1 mediate differential melanoma cell attachment to organ tissue sections in vitro and that differences in integrin expression of these melanoma cells may be involved in differential organ colonization in vivo.
近期数据表明，器官的细胞外基质和肿瘤细胞异质性整合素表达可能影响转移分布。
对三种人黑色素瘤细胞系进行整合素表达、与不同器官冷冻切片的体外结合以及在三重免疫缺陷小鼠中产生实验性转移能力的表征。
这三种细胞系表现出整合素的异质性表达、与冷冻切片的结合以及器官定植。一种原发性黑色素瘤细胞系（PM-WK）未产生实验性转移，仅对少数器官组织切片有少量或轻度附着，且所检测的α整合素亚基（VLA 1-6）和αvβ3表达缺失或极少。相比之下，两种淋巴结衍生细胞系表现出不同的器官定植模式：MM-RU仅定植于肺部，主要表达α2β1和αvβ3整合素，而MM-AN定植于肺部和肺外部位，包括胰腺和皮下棕色脂肪，主要表达α2β1和α6β1整合素。在体外，MM-RU对肺、棕色脂肪、肾脏和肾上腺有明显附着，对肝、胰腺、脑或肌肉组织切片无结合，而MM-AN具有类似的结合谱，但对肝和胰腺有额外附着。功能阻断抗β1单克隆抗体抑制MM-RU和MM-AN细胞对这些组织的附着（p < 0.001），而功能阻断抗α5和一种无关单克隆抗体（HLA I类）则无此作用。功能阻断抗α2单克隆抗体抑制MM-RU细胞黏附（p < 0.001），但不抑制MM-AN黏附。然而，功能阻断单克隆抗体α6β1显著抑制MM-AN与这些组织的结合。
这些数据表明，α2β1和α6β1在体外介导黑色素瘤细胞与器官组织切片的差异附着，且这些黑色素瘤细胞整合素表达的差异可能参与体内不同器官的定植。
