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Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer

Oncogene volume 22, pages 674–687 (2003)Cite this article

Abstract

Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with nonsmall cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that downregulation of several members of tetraspanins is associated with progression of solid tumors, thus indicating poor prognosis. Here we screened 30 lung cancer cell lines for expression of tetraspanins, CD9, CD63, CD81, CD82, CD151, and NAG-2. Flow cytometry revealed that, among these proteins, CD9 is broadly expressed in NSCLC lines, but is absent or highly reduced in most SCLC lines (P<0.0001). Using the Boyden chamber and videomicroscopic cell motility assays, we showed that stable transfection of CD9 into an SCLC line, OS3-R5, reduced cell motility on fibronectin. Furthermore, by transient transfection of green fluorescent protein (GFP)-tagged CD9 into three other SCLC lines, we observed that SCLC cells expressing GFP-CD9 were uniformly less motile than untransfected cells. CD9 or GFP-CD9 was associated with β1 integrins and distributed at the tumor cell periphery and cell–cell contacts, suggesting that CD9 modifies β1 integrin function to reduce motility. These findings suggest that low expression of CD9 may contribute to the highly invasive and metastatic phenotype of SCLC.

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Acknowledgements

This work was partially supported by a grant from Sankyo Foundation of Life Science, Tokyo, Japan, and by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan. The authors are grateful to Dr Martin E Hemler (Dana-Farber Cancer Institute, Boston) and Dr Osamu Yoshie (Kinki University School of Medicine, Osaka, Japan), for providing antibodies to tetraspanins. We also thank Yasuo Katsuki and Eiji Oiki (Osaka University Graduate School of Medicine) for technical assistance on the time-lapse videomicroscopic cell motility assay and Yoko Habe for secretarial assistance.

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Authors and Affiliations

  1. Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Sutia, Osaka, 565-0871, Japan

    Toshiki Funakoshi, Isao Tachibana, Hiromi Kimura, Yoshito Takeda, Kazumi Nishino, Hiroyuki Goto, Tsutomu Yoneda, Toru Kumagai, Tadashi Osaki, Seiji Hayashi & Ichiro Kawase

  2. Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Sutia, Osaka, 565-0871, Japan

    Yoshihiko Hoshida & Katsuyuki Aozasa

  3. Division of Thoracic and Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, 02115, MA, USA

    Takashi Kijima

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  1. Toshiki Funakoshi
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Correspondence to Isao Tachibana.

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Funakoshi, T., Tachibana, I., Hoshida, Y. et al. Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer. Oncogene 22, 674–687 (2003). https://doi.org/10.1038/sj.onc.1206106

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