A peptide binding to the tetraspanin CD9 reduces cancer metastasis

Thanawat Suwatthanarak; Kazuma Ito; Masayoshi Tanaka; Kei Sugiura; Ayuko Hoshino; Yoshitaka Miyamoto; Kenji Miyado; Mina Okochi

doi:10.1016/j.bioadv.2023.213283

A peptide binding to the tetraspanin CD9 reduces cancer metastasis

Biomater Adv. 2023 Mar:146:213283. doi: 10.1016/j.bioadv.2023.213283. Epub 2023 Jan 6.

Authors

Thanawat Suwatthanarak¹, Kazuma Ito², Masayoshi Tanaka³, Kei Sugiura⁴, Ayuko Hoshino⁴, Yoshitaka Miyamoto⁵, Kenji Miyado⁵, Mina Okochi⁶

Affiliations

¹ Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan; Siriraj Cancer Center, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok 10700, Thailand; Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok 10700, Thailand.
² Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan.
³ Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan; Department of Chemical Science and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan.
⁴ School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan.
⁵ Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
⁶ Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan. Electronic address: [email protected].

PMID: 36640525
DOI: 10.1016/j.bioadv.2023.213283

Abstract

As an organizer of multi-molecular membrane complexes, the tetraspanin CD9 has been implicated in a number of biological processes, including cancer metastasis, and is a candidate therapeutic target. Here, we evaluated the suppressive effects of an eight-mer CD9-binding peptide (CD9-BP) on cancer cell metastasis and its mechanisms of action. CD9-BP impaired CD9-related functions by adversely affecting the formation of tetraspanin webs-networks composed of CD9 and its partner proteins. The anti-cancer metastasis effect of CD9-BP was evidenced by the in vitro inhibition of cancer cell migration and invasion as well as exosome secretion and uptake, which are essential processes during metastasis. Finally, using a mouse model, we showed that CD9-BP reduced lung metastasis in vivo. These findings provide insight into the mechanism by which CD9-BP inhibits CD9-dependent functions and highlight its potential application as an alternative therapeutic nano-biomaterial for metastatic cancers.

Keywords: CD9; Cancer; Metastasis; Peptide; Tetraspanins.

MeSH terms

Humans
Neoplasm Metastasis
Neoplasms* / pathology
Neoplasms* / therapy
Oligopeptides* / metabolism
Oligopeptides* / therapeutic use
Tetraspanin 29* / metabolism

Substances

CD9 protein, human
Tetraspanin 29
Oligopeptides