Keratin 19 downregulation by oral squamous cell carcinoma lines increases invasive potential
Keratin 19 downregulation by oral squamous cell carcinoma lines increases invasive potential
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DOI：
10.1177/00220345990780061001
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发表时间：
1999-06-01
影响因子：
7.6
通讯作者：
Shuler, CF
中科院分区：
文献类型：
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作者：
Crowel, DL;Milo, GE;Shuler, CF
头颈部鳞状细胞癌 (SCC) 是全球第六大常见癌症。其生存率是主要癌症中最低的之一，并且在过去二十年中没有显着改善。广泛的局部侵袭和区域淋巴结转移在很大程度上是这些肿瘤临床结果不佳的原因。角蛋白中间丝是鳞状细胞癌中最丰富的细胞骨架蛋白，调节正常和转化上皮细胞的迁移。先前的研究表明，口腔上皮细胞中 40 kDa 角蛋白 K19 的表达失调。免疫组织化学实验表明，虽然正常上皮和发育异常病变表达丰富的 K19 蛋白，但侵袭性 SCC 表现出斑片状或阴性染色模式。我们随后确定，与正常上皮相比，K19 表达在七个 SCC 系中持续下调。因此，我们想确定 K19 下调是否影响这些细胞的侵袭表型。我们发现不表达 K19 的 SCC 系比保留该基因表达的 SCC 系更具体外侵袭性。 K19 阴性细胞系中 K19 cDNA 的稳定表达改变了细胞形态和细胞间粘附性，并显着减少了能够通过重建基底膜迁移的细胞数量。侵袭性降低并不是由于表达 K19 的克隆中金属蛋白酶活性降低所致。我们得出的结论是，口腔鳞状细胞癌中 K19 的过度表达通过降低迁移能力来降低其侵袭潜力。
Squamous cell carcinoma (SCC) of the head and neck is the sixth most frequent cancer worldwide. The survival rate is among the lowest of the major cancers and has not improved significantly in the past two decades. Extensive local invasion and regional lymph node metastasis are, in large part, responsible for the poor clinical outcome of these tumors. Keratin intermediate filaments are the most abundant cytoskeletal proteins in SCCs and regulate the migration of normal and transformed epithelial cells. Previous studies have shown that expression of the 40-kDa keratin K19 is dysregulated in SCCs arising from oral epithelium. Immunohistochemical experiments demonstrated that, while normal epithelium and dysplastic lesions expressed abundant K19 protein, invasive SCCs exhibited a patchy or negative staining pattern. We subsequently determined that K19 expression was consistently downregulated in seven SCC lines compared with normal epithelium. We therefore wanted to determine if K19 downregulation affected the invasive phenotype of these cells. We found that SCC Lines which do not express K19 are significantly more invasive in vitro than those which retain expression of this gene. Stable expression of the K19 cDNA in K19 negative cell lines altered cell morphology and intercellular adhesiveness, and significantly decreased the number of cells able to migrate through a reconstituted basement membrane. Reduced invasiveness was not due to decreased metalloproteinase activity in the K19-expressing clones. We conclude that K19 overexpression in oral SCCs decreases their invasive potential by diminishing migratory capability.