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Science 18 March 2005:
Vol. 307. no. 5716, pp. 1773 - 1776
DOI: 10.1126/science.1106209
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Reports

Type VII Collagen Is Required for Ras-Driven Human Epidermal Tumorigenesis

Susana Ortiz-Urda,1,2 John Garcia,1,2 Cheryl L. Green,1,2 Lei Chen,1,2 Qun Lin,1,2 Dallas P. Veitch,1,2 Lynn Y. Sakai,3 Hyangkyu Lee,1,2 M. Peter Marinkovich,1,2 Paul A. Khavari1,2*

Type VII collagen defects cause recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder often accompanied by epidermal cancers. To study the role of collagen VII in these cancers, we examined Ras-driven tumorigenesis in RDEB keratinocytes. Cells devoid of collagen VII did not form tumors in mice, whereas those retaining a specific collagen VII fragment (the amino-terminal noncollagenous domain NC1) were tumorigenic. Forced NC1 expression restored tumorigenicity to collagen VII–null epidermis in a non–cell-autonomous fashion. Fibronectin-like sequences within NC1 (FNC1) promoted tumor cell invasion in a laminin 5–dependent manner and were required for tumorigenesis. Tumor-stroma interactions mediated by collagen VII thus promote neoplasia, and retention of NC1 sequences in a subset of RDEB patients may contribute to their increased susceptibility to squamous cell carcinoma.

1 VA Palo Alto Healthcare System, Palo Alto, CA 94304, USA.
2 Program in Epithelial Biology, 269 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305, USA.
3 Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97201, USA

* To whom correspondence should be addressed. E-mail: khavari{at}cmgm.stanford.edu

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