Kitami Kazuhisa, Yoshihara Masato, Koya Yoshihiro, Sugiyama Mai, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Tano Sho, Fujimoto Hiroki, Nawa Akihiro, Kikkawa Fumitaka, Kajiyama Hiroaki
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Int J Mol Sci. 2020 Dec 21;21(24):9776. doi: 10.3390/ijms21249776.
Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.
卵巢癌（OvCa）因其向腹膜的高转移率而成为主要死因之一。尽管使用了传统的铂类化疗，但复发性腹膜肿瘤仍会发生。因此，探索与腹膜转移相关的因素仍然很重要，因为这些因素可以预测卵巢癌患者的预后。在本研究中，我们调查了小眼相关转录因子（MITF）在上皮性卵巢癌（OvCa）中的作用，MITF在黑色素瘤的发生发展中起作用。MITF高表达与卵巢癌的不良预后显著相关。值得注意的是，MITF促进了卵巢癌细胞的运动和侵袭，特别是它们在间皮周围的迁移。此外，MITF阳性细胞表达黑色素瘤细胞粘附分子（MCAM/CD146），该分子最初被确定为黑色素瘤进展和转移的标志物，且MCAM的表达受MITF调控。MCAM也被确定为卵巢癌患者无进展生存期不佳的一个重要预后因素。总的来说，我们的结果表明，MITF是一个潜在促进卵巢癌腹膜转移的新治疗靶点。
