Opposite regulation of tenascin-C and tenascin-X in MeLiM swine heritable cutaneous malignant melanoma

Opposite regulation of tenascin-C and tenascin-X in MeLiM swine heritable cutaneous malignant melanoma
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DOI:
10.1016/s0304-4165(00)00158-6
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发表时间:
2000-12-15
影响因子:
3
通讯作者:
Vielh, P
Vielh, P
中科院分区:
生物学3区
文献类型:
--
作者:
Geffrotin, C;Horak, V;Vielh, P

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肿瘤细胞与周围细胞外基质(ECM)之间的相互作用影响肿瘤细胞的生长及其转移能力。因此比较肿瘤和健康组织中的ECM组成是很有趣的。利用新近建立的MeLiM猪遗传皮肤恶性黑色素瘤模型,我们研究了两种ECM糖蛋白tenascin-C (TNC)和tenascin-X (TN-X)在正常皮肤和黑色素瘤中的表达。使用半定量RT-PCR,我们观察到黑色素瘤中TN-C rna比正常皮肤平均增加3.6倍。基质细胞和肿瘤细胞都能合成TN-C。相反,n - x rna在黑色素瘤中平均减少了30倍。通过间接免疫荧光在蛋白水平证实了对TN-C和TN-X rna的相反调节。猪正常皮肤在真皮-表皮交界处、血管和毛球周围表现出离散的TN-C信号,而猪肿瘤在这些区域以及基质和肿瘤细胞周围表现出增强的TN-C表达。相比之下,正常皮肤在真皮-表皮交界处和真皮层显示强烈的TN-X染色,而在肿瘤中这种信号几乎完全消失。本文的结果描述了猪恶性黑色素瘤中ECM组成的显著改变,这可能对肿瘤发生或黑色素瘤细胞的侵袭和转移有很大影响。(C) 2000 Elsevier Science B.V.版权所有
Interactions between tumour cells and surrounding extracellular matrix (ECM) influence the growth of tumour cells and their ability to metastasise. It is thus interesting to compare ECM composition in tumours and healthy tissues. Using the recently described MeLiM miniature pig model of heritable cutaneous malignant melanoma, we studied the expression of two ECM glycoproteins, the tenascin-C (TNC) and tenascin-X (TN-X), in normal skin and melanoma. Using semiquantitative RT-PCR, we observed a 3.6-fold mean increase of TN-C RNAs in melanoma compared to normal skin. Both stromal and tumour cells synthesise TN-C. On the contrary, TN-X RNAs decreased 30-fold on average in melanoma. This opposite regulation of TN-C and TN-X RNAs was confirmed at the protein level by indirect immunofluorescence. Whereas pig normal skin displayed a discrete TN-C signal at the dermo-epidermal junction, around blood vessels and hair bulbs, the swine tumour showed enhanced expression of TN-C in these areas and around stromal and tumour cells. In contrast, normal skin showed a strong TN-X staining at the dermo-epidermal junction and in the dermis, whereas this signal almost completely disappeared in the tumour. The results presented here describe a dramatic alteration of the ECM composition in swine malignant melanoma which might have a large influence on tumourigenesis or invasion and metastasis of melanoma cells. (C) 2000 Elsevier Science B.V. All rights reserved.