Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer
Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer
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DOI：
10.1007/s00403-004-0481-4
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发表时间：
2004-04-01
影响因子：
3
通讯作者：
Schön, MP
中科院分区：
文献类型：
--
作者：
Drewniok, C;Wienrich, BG;Schön, MP
恶性肿瘤通过周围组织进展的分子事件在很大程度上是由膜结合的黏附分子介导的。基底细胞黏附分子(B-CAM)是免疫球蛋白超家族的一种90 kDa的层粘连蛋白受体，在一些上皮性恶性肿瘤中被诱导表达。然而，它在这些肿瘤中的作用仍然不清楚。我们发现，B-CAM在正常皮肤表皮中的表达非常弱，但在皮肤的基底细胞癌和鳞状细胞癌中都有强烈的诱导，最明显的是在肿瘤巢的基底面。有趣的是，唯一已知的B-CAM配体，层粘连蛋白，在肿瘤巢周围相应的显微解剖位置显著上调，表明这两个分子可能在那里相互作用。与这一假设一致，我们能够直接证明B-CAM/Fc嵌合分子与瘤周基质的原位结合。最后，在原理验证实验中，人的B-CAM在小鼠和人成纤维细胞中都过表达。当二价阳离子的螯合作用阻断整合素介导的黏附时，这些新的B-CAM(+)细胞群在层粘连蛋白基质上的向肝细胞的迁移显著增加(P=0.02)。因此，我们的发现提供了第一个直接的实验证据，即B-CAM和层粘连蛋白的相互作用可能参与了上皮性皮肤肿瘤的进展。
Molecular events underlying the progression of malignant tumors through the surrounding tissue are largely mediated by membrane-bound adhesion molecules. Basal-cell adhesion molecule (B-CAM), a 90-kDa laminin receptor of the immunoglobulin superfamily, is induced in some epithelial malignancies. Its function in these tumors, however, still remains obscure. We demonstrated that expression of B-CAM is very weak, if detectable at all, in normal epidermis but is strongly induced in both basal cell carcinomas and squamous cell carcinomas of the skin, and most pronounced at the basal surface of the tumor nests. Interestingly, the only known B-CAM ligand, laminin, was markedly upregulated within corresponding microanatomical sites surrounding the tumor nests, suggesting that both molecules may interact there. Consistent with this hypothesis, we were able to directly demonstrate binding of a B-CAM/Fc chimeric molecule to the peritumoral stroma in situ. Finally, in proof-of-principle experiments, human B-CAM was overexpressed both in murine and in human fibroblasts. The haptotactic migration of these novel B-CAM(+) cell populations on a laminin matrix was significantly increased (P=0.02) as compared to mock-transfected cells when integrin-mediated adhesion was blocked by chelation of divalent cations. Thus, our findings provide the first direct experimental evidence that interactions of B-CAM and laminin may be involved in progression of epithelial skin tumors.