Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium
Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium
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DOI：
10.1038/labinvest.2008.15
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发表时间：
2008-05-01
影响因子：
5
通讯作者：
Okada, Morihito
中科院分区：
文献类型：
--
作者：
Ito, Akihiko;Hagiyama, Man;Okada, Morihito
细胞粘附分子 1 (CADM1) 以前称为 SgIGSF、TSLC1 或 Necl-2，已被定性为肥大细胞粘附分子，可介导与间皮细胞的有效相互作用。在这里，我们检查了 CADM1 是否可能参与胸膜表面弥漫性肿瘤生长，这是恶性胸膜间皮瘤 (MPM) 的特征。免疫组织化学和蛋白质印迹分析显示，57 个 MPM 中有 14 个（25%）在细胞膜上表达全长形式的 CADM1，但非肿瘤性间皮细胞根本不表达它。大多数可用的 MPM 细胞系也表达 CADM1 的全长形式。我们比较了在软琼脂内培养和在间皮或成纤维细胞单层上共培养的CADM1阳性和阴性MPM细胞。在软琼脂内，CADM1阴性MPM细胞能够形成集落，而CADM1阳性细胞则不能，这表明CADM1是MPM的潜在肿瘤抑制因子，这与该分子在其他类型肿瘤中的过去特征一致。然而，在缺乏全长CADM1的间皮细胞单层上的共培养中，CADM1阳性MPM细胞扩散得更广泛并且生长得更快，而CADM1阴性细胞则堆积起来。用CADM1 cDNA转染CADM1阴性细胞使它们表现得像CADM1阳性细胞一样，生长更快、更广泛。这些表型差异在肺成纤维细胞单层共培养中无法检测到，其中所有 MPM 细胞的生长速度都比间皮细胞慢得多，无论 CADM1 是否呈阳性。因此，CADM1似乎介导MPM细胞在间皮细胞上的有效粘附和生长，可能是通过反式异嗜性结合，因此可能涉及相当大的MPM子集作为在胸膜表面播散的弥漫性生长肿瘤的表现。
Cell adhesion molecule 1 (CADM1), formerly referred to as SgIGSF, TSLC1, or Necl-2, has been characterized as a mast-cell adhesion molecule that mediates efficient interactions with mesothelial cells. Here, we examined whether CADM1 might be involved in the diffuse tumor growth over the pleural surface that characterizes malignant pleural mesothelioma (MPM). Immunohistochemical and western blot analyses revealed that 14 (25%) of 57 MPMs expressed the full-length form of CADM1 on the cell membrane, but non-neoplastic mesothelial cells did not express it at all. The majority of available MPM cell lines also expressed the full-length form of CADM1. We compared CADM1-positive and -negative MPM cells in culture within soft agar and in coculture on mesothelial or fibroblastic monolayers. Within soft agar, CADM1-negative MPM cells were capable of forming colonies, whereas CADM1-positive cells were not, suggesting that CADM1 is a potential tumor suppressor of MPM, consistent with the past characterization of this molecule in other types of tumors. However, in coculture on mesothelial cell monolayers lacking full-length CADM1, CADM1-positive MPM cells spread more widely and grew more quickly, whereas the CADM1-negative cells piled up. Transfection of the CADM1-negative cells with CADM1 cDNA caused them to behave like the CADM1-positive cells, with faster, more widespread growth. These phenotypic differences were not detectable in cocultures on lung fibroblastic monolayers, in which all MPM cells grew much more slowly than on mesothelial cells, irrespective of CADM1 positivity. CADM1 thus appears to mediate efficient adhesion and growth of MPM cells specifically on mesothelial cells, probably via trans-heterophilic binding, and thus may be involved in the manifestation of a considerable subset of MPMs as diffusely growing tumors disseminated over the pleural surface.