Fujimaki T, Price J E, Fan D, Bucana C D, Itoh K, Kirino T, Fidler I J
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Melanoma Res. 1996 Oct;6(5):363-71. doi: 10.1097/00008390-199610000-00003.
The purpose of this study was to determine whether the growth of human melanoma cells in the brain parenchyma is selective and represents the growth of unique cells. Six human melanoma cell lines derived from cutaneous lymph node or brain metastases (from six different patients) and melanoma cells isolated from fresh surgical specimens of two primary cutaneous melanomas, two lymph node metastases and two brain metastases (each from a different patient) were injected into the subarachnoid space of nude mice. All melanomas produced growths in the leptomeninges, but only melanoma cells isolated from brain metastases infiltrated into and grew in the brain parenchyma of nude mice. The results from in vitro assays for cell motility or production of gelatinase activity did not correlate with in vivo growth pattern. However, the in vitro growth of human melanoma cells in the presence of TGF-beta 2 inversely correlated with potential for brain parenchyma metastasis, i.e. the growth of cells from brain metastases was least inhibited by TGF-beta 2. These data suggest that melanoma brain parenchyma metastases are produced by unique cells that may be resistant to the antiproliferative effects of TGF-beta 2.
本研究的目的是确定人脑实质中人类黑色素瘤细胞的生长是否具有选择性,以及是否代表独特细胞的生长。将源自皮肤淋巴结或脑转移瘤(来自六个不同患者)的六种人类黑色素瘤细胞系,以及从两例原发性皮肤黑色素瘤、两例淋巴结转移瘤和两例脑转移瘤(各来自不同患者)的新鲜手术标本中分离出的黑色素瘤细胞,注射到裸鼠的蛛网膜下腔。所有黑色素瘤均在软脑膜中生长,但只有从脑转移瘤中分离出的黑色素瘤细胞浸润并在裸鼠的脑实质中生长。细胞运动性或明胶酶活性产生的体外试验结果与体内生长模式无关。然而,在转化生长因子β2存在的情况下,人类黑色素瘤细胞的体外生长与脑实质转移潜能呈负相关,即来自脑转移瘤的细胞生长受转化生长因子β2的抑制最小。这些数据表明,黑色素瘤脑实质转移是由可能对转化生长因子β2的抗增殖作用具有抗性的独特细胞产生的。