INVOLVEMENT OF INTEGRIN ALPHA-V GENE-EXPRESSION IN HUMAN-MELANOMA TUMORIGENICITY
INVOLVEMENT OF INTEGRIN ALPHA-V GENE-EXPRESSION IN HUMAN-MELANOMA TUMORIGENICITY
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DOI：
10.1172/jci115811
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发表时间：
1992-06-01
影响因子：
15.9
通讯作者：
CHERESH, DA
中科院分区：
文献类型：
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作者：
FELDINGHABERMANN, B;MUELLER, BM;CHERESH, DA
人类黑色素瘤起源于皮肤，可导致广泛的转移性疾病。黑色素瘤活检材料的分析表明，玻连蛋白受体，整合素-α-v-β-3，是最恶性细胞的特异性标志物，即，垂直侵入性原发病灶或远处转移（Albelda，S. M.，S. A. Mette，D. E.埃尔德河，西-地斯图尔特湖Damjanovich，M. Herlyn和C. A.巴克1990. Cancer Res. 50：6757-6764），表明该粘附受体在人黑素瘤肿瘤的恶性生长中的作用。建立了一个细胞模型，以分析α-v整合素在人黑色素瘤致瘤性中的作用。从M21人黑素瘤细胞中，选择缺乏α-v基因表达并因此不能表达整联蛋白-α-v-β-3的稳定变体（M21-t细胞）。这些细胞不仅失去了附着到玻连蛋白的能力，而且与M21细胞相比，当移植到无胸腺裸鼠中时，致瘤性显着降低，即使两种细胞类型在体外显示出相同的β-1整合素表达和生长特性。用编码α-v的cDNA稳定转染M21-L细胞。这导致这些细胞上整合素-α-v-β-3的功能性表达，并完全恢复其致瘤性。因此，整合素-α-v基因表达和由此产生的粘附表型直接参与体内人黑素瘤的增殖。
Human melanoma originates in the skin and can lead to widespread metastatic disease. Analysis of melanoma biopsy material has shown that the vitronectin receptor, integrin-alpha-v-beta-3, is a specific marker of the most malignant cells, i.e., vertically invasive primary lesions or distant metastases (Albelda, S. M., S. A. Mette, D. E. Elder, R. Stewart, L. Damjanovich, M. Herlyn, and C. A. Buck. 1990. Cancer Res. 50:6757-6764), suggesting a role for this adhesion receptor in the malignant growth of human melanoma tumors. A cell model was established to analyze the role of alpha-v integrins on the tumorigenicity of human melanoma. From M21 human melanoma cells, stable variants were selected that lack alpha-v gene expression and thus fail to express integrin-alpha-v-beta-3 (M21-t, cells). These cells not only lost the ability to attach to vitronectin but showed a dramatic reduction in tumorigenicity when transplanted into athymic nude mice, compared with M21 cells, even though both cell types showed identical beta-1 integrin expression and growth properties in vitro. M21-L cells were stably transfected with a cDNA-encoding alpha-v. This resulted in the functional expression of integrin-alpha-v-beta-3 on these cells and completely restored their tumorigenicity. Thus, integrin-alpha-v gene expression and the resulting adhesive phenotype are directly involved in the proliferation of human melanoma in vivo.