Schmid P, Itin P, Rufli T
Department of Dermatology, University Basel, Switzerland.
Carcinogenesis. 1995 Jul;16(7):1499-503. doi: 10.1093/carcin/16.7.1499.
We have analysed, by in situ hybridization, mRNA expression of TGF-beta 1, TGF-beta 2, TGF-beta 3, and of TGF-beta type II receptor in benign melanocytic naevi, primary melanomas, and in skin metastases of malignant melanomas. Our results show that melanoma progression correlates with overexpression of TGF-beta. All skin metastases and most primary melanomas invasive to Clark's level IV-V revealed specific TGF-beta 2 mRNA and protein expression. However, expression of this cytokine was not observed in benign melanocytic lesions and was detected only in one of five early primary melanomas investigated. Some primary melanomas and skin metastases also revealed specific TGF-beta 1 mRNA signals although expression of this isoform was not found in benign naevi. TGF-beta 3 expression, which was only barely detectable in benign melanocytic lesions, was enhanced in some skin metastases. Interestingly, the epidermis overlaying melanomas revealed lower levels of TGF-beta 3 mRNA expression than epidermis of healthy skin or epidermis adjacent to benign naevi, thereby suggesting that paracrine mechanisms between tumour cells and keratinocytes may influence melanoma development. In primary melanomas TGF-beta type II receptor mRNA signals were much more heterogeneously distributed when compared to benign melanocytic naevi, suggesting variable degrees of TGF-beta resistance among melanoma cells within individual lesions. However, melanoma progression appeared not to be correlated with a complete loss of TGF-beta type II receptor gene expression, since all skin metastases revealed clearly detectable although heterogeneous levels of TGF-beta type II receptor mRNA expression.
我们通过原位杂交分析了良性黑素细胞痣、原发性黑色素瘤以及恶性黑色素瘤皮肤转移灶中转化生长因子β1（TGF-β1）、转化生长因子β2（TGF-β2）、转化生长因子β3（TGF-β3）和转化生长因子βⅡ型受体的mRNA表达情况。我们的结果表明，黑色素瘤的进展与TGF-β的过表达相关。所有皮肤转移灶以及大多数浸润至Clark分级Ⅳ-Ⅴ级的原发性黑色素瘤均显示出特异性的TGF-β2 mRNA和蛋白表达。然而，在良性黑素细胞病变中未观察到这种细胞因子的表达，在所研究的5例早期原发性黑色素瘤中仅1例检测到。一些原发性黑色素瘤和皮肤转移灶也显示出特异性的TGF-β1 mRNA信号，尽管在良性痣中未发现该亚型的表达。TGF-β3的表达在良性黑素细胞病变中仅勉强可检测到，在一些皮肤转移灶中增强。有趣的是，覆盖黑色素瘤的表皮显示出的TGF-β3 mRNA表达水平低于健康皮肤的表皮或与良性痣相邻的表皮，从而提示肿瘤细胞与角质形成细胞之间的旁分泌机制可能影响黑色素瘤的发展。与良性黑素细胞痣相比，原发性黑色素瘤中TGF-βⅡ型受体mRNA信号的分布更加不均一，提示单个病变内的黑色素瘤细胞之间存在不同程度的TGF-β抵抗。然而，黑色素瘤的进展似乎与TGF-βⅡ型受体基因表达的完全缺失无关，因为所有皮肤转移灶均显示出明显可检测到的、尽管水平不均一的TGF-βⅡ型受体mRNA表达。
