To identify molecular markers for the progression of headand-neck squamous cell carcinoma (HNSCC), we used RNA arbitrarily primed (RAP) PCR to determine the qualitative and quantitative differences in gene expression between normal epithelial cells, those derived from dysplastic oral mucosa and invasive and metastatic HNSCC. Three differentially expressed DNA fragments (RAP20, RAP21, RAP26) that were upregulated in a tumor cell line (T45) were identified as being regions of the ␥2 subunit of human laminin-5. Northern blot analysis of total cellular RNA revealed overexpression of these transcripts in 6 of 7 HNSCC cell lines compared with normal epidermal keratinocytes. In contrast, no differences were observed in HeLa (cervical carcinoma) or HCT116 (colon carcinoma) cells. Laminin is a major component of the basement membrane, which performs multiple biologic roles, including cell attachment, spreading and migration as well as being involved in cellular proliferation and differentiation. 1,2 Structurally, laminin is a heterotrimeric protein comprising ␣,  and ␥ subunits, of which several variants exist. 3 Thus, different subunit combinations result in a family of laminins. 3,4 Specific biologic activities of different laminins may be reflected in the fact that these molecules show tissue-specific expression. For example, laminin-5 is considered to be an epithelial laminin as it is found as a component of basement membranes in epithelial tissues but not in mesenchyme. 5,6 Furthermore, cytokines that regulate epithelial homeostasis, such as transforming growth factor (TGF)-, modulate the expression of laminin-5 polypeptides in epidermal keratinocytes. 7 A role for laminin isoforms in tumor cell invasion is becoming apparent. 8 For instance, attachment of cancer cells is mediated in part by laminins. 9,10 Additionally, increased cell-surface expression of laminin was found in highly metastatic fibrosarcoma cells compared to cells of low metastatic potential. 11 Furthermore, expression and activity of matrix metalloproteases, which play critical roles in cellular invasion, are elevated in the presence of laminin, 12 and metastasis of melanoma cells is also enhanced. 13 Further studies have demonstrated that attachment and metastasis of tumor cells can be inhibited by incubation with antilaminin antibodies 14,15 or synthetic laminin peptides. 16 Several reports have implicated laminin-5 in epithelial tumor cell invasion. In one study, overexpression of the ␥2 chain of laminin-5 was found in 26 of 27 carcinomas, while various mesenchymal tumors did not express this molecule. 17 Furthermore, the highest expression of ␥2 occurred at areas of active invasion in colon adenocarcinomas, and a clear correlation was found with tumor budding. 17 In a subsequent study, these findings were extended to examine expression in a larger series of human cancers, 18 demonstrating that levels of ␥2 were indeed the highest in squamous carcinomas, particularly in cells adjacent to surrounding stromal tissue and in deeply invading cell ne...
Contents of this paper were reviewed by the Technical Committee of the 16 th International Congress of the Brazilian Geophysical Society and do not necessarily represent any position of the SBGf, its officers or members. Electronic reproduction or storage of any part of this paper for commercial purposes without the written consent of the Brazilian Geophysical Society is prohibited.
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