Extracellular matrix receptors and mouse skin carcinogenesis: altered expression linked to appearance of early markers of tumor progression.
Extracellular matrix receptors and mouse skin carcinogenesis: altered expression linked to appearance of early markers of tumor progression.
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发表时间：
1992-05
期刊：
影响因子：
11.2
通讯作者：
T. Tennenbaum;S. Yuspa;A. Grover;V. Castronovo;M. Sobel;Yoshihiko Vainada;L. M. Luca
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文献类型：
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作者：
T. Tennenbaum;S. Yuspa;A. Grover;V. Castronovo;M. Sobel;Yoshihiko Vainada;L. M. Luca
细胞与基底膜的相互作用对于细胞增殖和分化是重要的。基底膜的破坏是良性肿瘤发展为癌症的早期事件。使用免疫组织化学和免疫荧光技术，我们表明，通过细胞表面整合素受体α 3 β 1，α 5 β 1，α 6 β 4，Mr 67，000层粘连蛋白受体（67 LR）层粘连蛋白结合蛋白，和分泌的基质蛋白层粘连蛋白的细胞-基质相互作用在小鼠表皮分化过程中受到严格调控。虽然α 6 β 4和α 5 β 1被极化到与基底膜接触的基底细胞的基底表面，α 3 β 1和非整合素67 LR主要在基底上细胞的细胞外周中检测到，在那里发现细胞与细胞的接触。在对化学致癌物或癌基因转导诱导的良性和恶性皮肤肿瘤的分析中，我们发现α 3 β 1和α 5 β 1以及非整合素67 LR在从良性到恶性的进展中依次下调，而α 6 β 4是癌中表达的主要受体。α 6 β 4的肿瘤表达不是极化的，并且与其共定位的正常伴侣大疱性类天疱疮抗原分离，后者仍然局限于基底膜。基质受体的变化与基底上区角蛋白13的出现有关，但总是在α 6 β 4阴性细胞中。在进展过程中，α 6 β 4在增殖细胞中的优势与癌中角蛋白13的表达降低相关。这些结果表明，基质与其受体的相互作用是正常皮肤有序分化的重要决定因素，并在癌变过程中表现出与肿瘤分化变化平行的特征性改变。
Interaction of cells with the basement membrane is important for cell proliferation and differentiation. Disruption of the basement membrane is an early event during progression of benign tumors to cancer. Using the techniques of immunohistochemistry and immunofluorescence, we show that cell-matrix interactions via the cell surface integrin receptors alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 4, the Mr 67,000 laminin receptor (67LR) laminin-binding protein, and the secreted matrix protein laminin are strictly regulated during differentiation of mouse epidermis. While alpha 6 beta 4 and alpha 5 beta 1 are polarized to the basal surface of basal cells in contact with the basement membrane, alpha 3 beta 1 and the non-integrin 67LR are primarily detected in the cell periphery of suprabasal cells, where cell to cell contacts are found. Sequential changes in expression of matrix receptors occur following multistage carcinogenesis of mouse skin. In an analysis of benign and malignant skin tumors induced by chemical carcinogens or oncogene transduction, we found that alpha 3 beta 1 and alpha 5 beta 1 as well as the non-integrin 67LR are sequentially down-regulated in the progression from benign to malignant, while alpha 6 beta 4 is the predominant receptor expressed in the carcinomas. Tumor expression of alpha 6 beta 4 is not polarized and is dissociated from its colocalized normal partner bullous pemphigoid antigen, which remains restricted to the basement membrane. The changes in matrix receptors are linked to appearance of keratin 13 in suprabasal regions, but always in alpha 6 beta 4 negative cells. The predominance of alpha 6 beta 4 in the proliferating cells during progression is associated with decreased expression of keratin 13 in carcinomas. These results suggest that matrix interactions with its receptors are important determinants of ordered differentiation in normal skin and show characteristic alterations during carcinogenesis that parallel changes in differentiation of the tumors.