Expression of laminin 5-γ2 chain in cutaneous squamous cell carcinoma and its role in tumour invasion

Abstract

Background: Laminin-5 (Ln5), a heterotrimer composed of three chains (α3, Β3, and γ2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-γ2, is a marker of invasive tumours because it is frequently expressed as a monomer in malignant tumours. Recent studies from our laboratories detected higher levels of Ln5-γ2 expression in basal cell carcinoma (BCC) than in trichoblastoma. Furthermore, Ln5-γ2 overexpression tended to correlate with aggressiveness in BCC. Methods: In this study, we compared the expression of Ln5-γ2 in invasive squamous cell carcinoma (SCC, n62) of the skin to that in preinvasive Bowens disease (BD, n51), followed by analysis of the role of Ln5-γ2 in cancer invasion in vitro. Results: Immunohistochemically, the proportion of SCC cases (86%) strongly positive for Ln5-γ2 expression was higher than that of BD (16%). Real-time RT-PCR showed Ln5-γ2 overexpression in SCC cell line, A431, compared with normal keratinocyte cell line, HaCaT. Ln5-γ2 monomer and proteolytically cleaved, biologically active fragments of Ln5-γ2 were identified in SCC tumour extracts. In in vitro raft cultures, which simulate in vivo conditions, Ln5-γ2 siRNA significantly suppressed epidermal growth factor (EGF)-stimulated A431 cell invasion. Conclusion: Our results indicate that Ln5-γ2 has a role in cutaneous SCC invasion. © 2011 Cancer Research UK All rights reserved.