J Cancer 2017; 8(11):2033-2041. doi:10.7150/jca.18714

Research Paper

Activin B Regulates Adhesion, Invasiveness, and Migratory Activities in Oral Cancer: a Potential Biomarker for Metastasis

Akihiro Kita1, Atsushi Kasamatsu2✉, Dai Nakashima1, Yosuke Endo-Sakamoto2, Sho Ishida1, Toshihiro Shimizu4, Yasushi Kimura5, Isao Miyamoto6, Shusaku Yoshimura1, Masashi Shiiba3, Hideki Tanzawa1,2, Katsuhiro Uzawa1,2✉

1. Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
3. Department of Medical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
4. Department of Dentistry and Oral-Maxillofacial Surgery, Kashima Rosai Hospital, 1-9108-2 Doaihoncho, Kamisu, Ibaraki 314-0343, Japan
5. Department of Dentistry and Oral-Maxillofacial Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
6. Department of Dentistry and Oral-Maxillofacial Surgery, Japanese Red Cross Fukaya Hospital, 5-6-1 Kamishibachonishi, Fukaya, Saitama, 366-0052 Japan

Abstract

Activin B, a homodimer of inhibin beta b (INHBB), is a multifunctional cytokine belonging to the transforming growth factor-β (TGF-β) family. However, the molecular functions and clinical relevance of activin B have not been determined in oral cancer. We investigated the critical roles of activin B in oral squamous cell carcinoma (OSCC). We performed quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry to study INHBB expression in OSCC-derived cell lines and OSCC clinical samples. The INHBB expression levels were significantly (P < 0.05) overexpressed in OSCCs compared to normal counterparts in vitro and in vivo. Activin B-positivity in OSCC cases was significantly (P < 0.05) correlated with regional lymph node metastasis. The INHBB knockdown (shINHBB) cells promoted cellular adhesion and suppression of cellular invasiveness and migration. After treatment of shINHBB cells with activin B, those activities were restored similar to the shMock cells. In the processes of invasiveness and metastasis, the cells cause epithelial-mesenchymal transition (EMT). TGF-β and its family members are promoters of the EMT process. To investigate whether activin B is related to EMT, we examined the expressions of EMT-related genes and found that INHBB was related closely to EMT. Our results suggested for the first time that activin B indicates tumoral metastasis in OSCCs and might be a useful biomarker for OSCC metastasis.

Keywords: activin B, inhibin beta b, INHBB, oral squamous cell carcinoma, metastasis.

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How to cite this article:
Kita A, Kasamatsu A, Nakashima D, Endo-Sakamoto Y, Ishida S, Shimizu T, Kimura Y, Miyamoto I, Yoshimura S, Shiiba M, Tanzawa H, Uzawa K. Activin B Regulates Adhesion, Invasiveness, and Migratory Activities in Oral Cancer: a Potential Biomarker for Metastasis. J Cancer 2017; 8(11):2033-2041. doi:10.7150/jca.18714. Available from http://www.jcancer.org/v08p2033.htm