AMIGO2 is involved in the spread of peritoneal metastasis in serous ovarian cancer via promoting adhesion to the peritoneal mesothelial cells

• Published in: International journal of clinical oncology 2024-09, Vol.29 (9), p.1354-1363
• Main Authors: Iida, Yuki, Osaki, Mitsuhiko, Sato, Shinya, Izutsu, Runa, Seong, HeeKyung, Komatsu, Hiroaki, Taniguchi, Fuminori, Okada, Futoshi
• Format: Article
• Language: English
• Subjects: Aged; Animal models; Animals; Cancer Research; Cell Adhesion; Cell Line, Tumor; Cervical cancer; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - pathology; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Oncology; Original Article; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Peritoneal Neoplasms - genetics; Peritoneal Neoplasms - secondary; Peritoneum; Peritoneum - pathology; Prognosis; Surgical Oncology; Tumor cell lines
• ISSN: 1341-9625; 1437-7772; 1437-7772
• DOI: 10.1007/s10147-024-02556-6

Background Amphoterin-induced gene and open reading frame 2 (AMIGO2) have been reported to be related to the prognosis of colorectal, gastric, and cervical cancer. However, their association with ovarian cancer remains unclear. This study aimed to elucidate the role of AMIGO2 in ovarian cancer. Methods AMIGO2 expression was evaluated using immunohistochemistry in patients with ovarian serous carcinoma. We validated in vitro studies using four serous ovarian cancer cell lines and in vivo studies using a murine model. Results The AMIGO2-high group had significantly shorter progression-free survival (PFS) than the AMIGO2-low group. The predictive index of the AMIGO2-high group was considerably higher than that of the AMIGO2-low group. The rate of complete cytoreductive surgery was lower in the AMIGO2-high group than in the AMIGO2-low group. Moreover, in vitro studies revealed that four serous ovarian cancer cell lines exhibited AMIGO2 expression and adhesion to mesothelial cells. Adhesion to mesothelial cells was attenuated by AMIGO2 knockdown in SKOV3 and SHIN3 cells. Furthermore, AMIGO2 downregulation in SKOV3 cells significantly suppressed peritoneal dissemination in the murine model. Conclusion These results suggest that high AMIGO2 expression in serous ovarian carcinoma cells contributes to a poor prognosis by promoting peritoneal metastasis through enhanced cell adhesion to mesothelial cells.