title: Integrin A6 Cleavage in Mouse Skin Tumors.
abstract: We have previously identified a structural variant of the α6 integrin (Laminin receptor) called α6p. The α6p variant is a 70 kDa form of the full-length α6 integrin (140 kDa) that remains paired with either the β1 or β4 subunit on the cell surface. α6p is produced by urokinase-type plasminogen activator (uPA), which removes the extracellular β-barrel domain while the receptor is on the cell surface. The α6p integrin was present in human prostate cancer tissue but not in normal tissue and the cleavage of the α6 integrin extracellular domain promotes tumor cell invasion and migration on laminin. The objective of the present study was to determine whether the α6p integrin is observed in other models of carcinogenesis. Our results indicate detectable low levels of α6p in normal mouse skin, and comparatively elevated levels in mouse papillomas and squamous cell carcinomas induced by DMBA, TPA and MNNG treatments. Furthermore, we have found that α6p was present at high levels in skin melanomas of transgenic mice that over express activated Ha-ras under the control of the tyrosinase promoter. Finally, subcutaneous injection into athymic nude mice of a malignant mouse keratinocyte derived cell line (6M90) that is α6p negative, results in the development of tumors that contain α6p integrin. The latter results indicate that α6p is induced in vivo suggesting that the tumor microenvironment plays a major role in the production of α6p. Taken together, these data suggest that the cell surface cleavage of the α6 integrin may be a novel mechanism of integrin regulation and might be an important step during skin tissue remodeling and during carcinogenesis.
authors.affiliation: Department of Biological Sciences, University of Cyprus, Cyprus.
authors.forename: Manolis C
authors.initials: MC
authors.lastname: Demetriou
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Kwei
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Powell
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Nagle
authors.forename: G Tim
authors.initials: GT
authors.lastname: Bowden
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cress