1. ¹Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, Japan
2. ²Department of Plastic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
3. ³Department of Biochemistry and Molecular Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan
4. ⁴Department of Oral and Maxillofacial Surgery, Kyushu University Hospital, Fukuoka, Japan
5. ⁵Department of Pathology, Jikei University School of Medicine, Tokyo, Japan
6. ⁶Department of Veterinary Medicine, Iwate University, Morioka, Japan

Correspondence: Dr M Furuya, MD, PhD, Department of Molecular Pathology, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan. E-mail: furuya@faculty.chiba-u.jp

^*These two authors contributed equally to this work.

Received 26 February 2007; Revised 6 June 2007; Accepted 8 June 2007; Published online 16 July 2007.

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 31 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. 31 integrin was internalized in part, and 64 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.