Stromal fibroblasts from basal cell carcinoma affect phenotype of normal keratinocytes
Stromal fibroblasts from basal cell carcinoma affect phenotype of normal keratinocytes
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DOI：
10.1111/j.1365-2133.2006.07728.x
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发表时间：
2007-05-01
影响因子：
10.3
通讯作者：
Andre, S.
中科院分区：
文献类型：
--
作者：
Lacina, L.;Smetana, K., Jr.;Andre, S.
上皮-间充质相互作用不仅对指导皮肤及其附属物的产前发育过程很重要，而且对转化上皮细胞的行为也有重要影响。目的探讨基质成纤维细胞在基底细胞癌（BCC）上皮细胞表型中的作用。方法采用体外模型，观察正常人角化细胞与BCC基质制备的成纤维细胞、正常真皮成纤维细胞或两种已建立的成纤维细胞系共培养时的生长和表型变化。我们可视化了一组角蛋白、三种内源性凝集素[galectin (Gal)-1、Gal-3和Gal-7]、Gal-1和Gal-3的结合位点、增殖标志物Ki67、核仁蛋白核干蛋白（NuclS）和膜蛋白Ber-EP4的表达。对BCCFs的表型和核型也进行了监测。BCCFs也被移植到NOD/LtSz-Rag1（null）小鼠中，以评估其恶性潜能。结果长时间培养BCCFs导致细胞形态改变、接触抑制丧失、成纤维细胞表面抗原丧失、非整倍性进展。然而，由于这些细胞在免疫缺陷小鼠中不形成肿瘤，因此没有形成完全的恶性表型。BCCFs与正常角质形成细胞体外共培养后，其表型变化与BCC相似，即角蛋白19的表达。这些角化细胞也强烈表达Gal-1和nucl的核结合位点。当正常角质形成细胞与非肿瘤来源的成纤维细胞一起培养时，没有观察到这种表型。结论BCCFs可能不同于正常成纤维细胞，并可能在BCCFs生物学中发挥调节作用。
Background Epithelial-mesenchymal interactions are important not only to direct the course of prenatal development of skin and its appendages but also to influence the behaviour of transformed epithelial cells.Objectives Evaluation of the role of stromal fibroblasts on the phenotype of epithelial cells of basal cell carcinoma (BCC).Methods The phenotype of human BCC was compared with the in vitro model where the growth and phenotypic pattern of normal human keratinocytes were monitored in co-culture with fibroblasts prepared from stroma of BCC (BCCFs), with normal dermal fibroblasts or with two established fibroblast lines. We visualized the expression of a panel of keratins, three types of endogenous lectin [galectin (Gal)-1, Gal-3 and Gal-7], binding sites for Gal-1 and Gal-3, a proliferation marker Ki67, nucleolar protein nucleostemin (NuclS) and membrane protein Ber-EP4. A phenotype and karyotype of BCCFs were also monitored. BCCFs were also grafted to NOD/LtSz-Rag1(null) mice to evaluate their malignant potential.Results Prolonged cultivation of BCCFs has led to morphological changes, loss of contact inhibition, loss of fibroblast surface antigens and progressive aneuploidity. However, a fully malignant phenotype did not develop as these cells did not form tumours in immunodeficient mice. Co-culture of BCCFs with normal keratinocytes in vitro led to their phenotypical changes resembling those in BCC, namely, expression of keratin 19. These keratinocytes also strongly express nuclear binding sites for Gal-1 and NuclS. This phenotype was not observed when normal keratinocytes were cultured with nontumour-originated fibroblasts.Conclusions These observations indicate that BCCFs may differ from normal fibroblasts and may play a regulatory role in BCC biology.