RRC ID 43043
Author Hasegawa M, Furuya M, Kasuya Y, Nishiyama M, Sugiura T, Nikaido T, Momota Y, Ichinose M, Kimura S.
Title CD151 dynamics in carcinoma-stroma interaction: integrin expression, adhesion strength and proteolytic activity.
Journal Lab Invest
Abstract A member of tetraspanin CD151 is a scaffold protein of laminin-binding integrins and it plays an important role in stable interaction between cells and basement membrane. Although the upregulation of CD151 in tumor cells is thought to accelerate tumor invasion and metastasis, detailed pathological investigation on CD151 and its association with integrins has not been well documented, yet. In the present study, we showed that the expression levels of CD151 and its associated integrin subunits in epidermal carcinoma cell HSC5 were higher than those in immortalized epidermal cell HaCaT. By the stimulation of epidermal growth factor, CD151 was dissociated from cell surface and dispersed in the cytoplasm, and alpha3beta1 integrin was concomitantly internalized. To understand the significance of CD151 in tumor cell dynamics, CD151 in HSC5 was knocked down (HSC5(CD151-)), and the expression of integrin subunits and matrix metalloproteinases (MMPs) were investigated. In HSC5(CD151-), striking morphological alteration on Matrigel and laminin, and cytoskeletal rearrangements were demonstrated. alpha3beta1 integrin was internalized in part, and alpha6beta4 integrin was re-distributed from basal site to cell periphery. Quantitative RT-PCR, Western blot and zymography revealed that the expression levels of MMP2, MMP7 and MMP9 were markedly downregulated in HSC5(CD151-). Immunoprecipitation assay demonstrated that MMP7 was co-immunoprecipitated with CD151. In double stainings, MMP7 was colocalized with CD151 at the leading edge of lamellipodia under migratory status. These results elucidated the importance of CD151 as one of the key molecules for integrin-dependent carcinoma-stroma interaction. It is indicated that CD151 might contribute not only to cell stabilization by associating with adhesion complexes but also to cell migration by inducing integrins re-localization and MMPs production.
Volume 87(9)
Pages 882-92
Published 2007-9-1
DOI 10.1038/labinvest.3700657
PII 3700657
PMID 17632541
MeSH Antigens, CD / metabolism* Carcinoma / physiopathology* Cell Adhesion / physiology* Cell Line, Tumor Cell Movement / physiology* Down-Regulation Extracellular Matrix / physiology Hemidesmosomes / physiology Humans Integrin alpha3beta1 / metabolism Integrin alpha6beta4 / metabolism Matrix Metalloproteinases, Secreted / metabolism Neoplasms, Squamous Cell / physiopathology* Stromal Cells / physiology Tetraspanin 24
IF 4.197
Times Cited 45
Human and Animal Cells HTOA(RCB0692)