In vivo selection of highly metastatic human ovarian cancer sublines reveals role for AMIGO2 in intra-peritoneal metastatic regulation. (10th April 2021)

• Record Type: Journal Article
• Authors: Liu, Yueying; Yang, Jing; Shi, Zonggao; Tan, Xuejuan; Jin, Norman; O'Brien, Catlin; Ott, Connor; Grisoli, Anna; Lee, Eric; Volk, Kelly; Conroy, Meghan; Franz, Emily; Bryant, Annamarie; Campbell, Leigh; Crowley, Brian; Grisoli, Stephen; Alexandrou, Aris T.; Li, Chunyan; Harper, Elizabeth I.; Asem, Marwa; Johnson, Jeff; Leonard, Annemarie; Santanello, Katie; Klein, Ashley; Wang, Qingfei; Zhang, Siyuan; Hilliard, Tyvette S.; Stack, M. Sharon
• Is Part Of: Cancer letters. Volume 503(2021)
• Page Start: 163
• Page End: 173
• Publication Date: 2021-04-10
• Subjects: Ovarian cancer -- Intra-peritoneal metastasis -- AMIGO2 -- Spheroid -- Multi-cellular aggregate -- Tumorsphere [deleted adhesion -- Invasion]; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.01.024
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: The majority of women with ovarian cancer are diagnosed with metastatic disease, therefore elucidating molecular events that contribute to successful metastatic dissemination may identify additional targets for therapeutic intervention and thereby positively impact survival. Using two human high grade serous ovarian cancer cell lines with inactive TP53 and multiple rounds of serial in vivo passaging, we generated sublines with significantly accelerated intra-peritoneal (IP) growth. Comparative analysis of the parental and IP sublines identified a common panel of differentially expressed genes. The most highly differentially expressed gene, upregulated by 60-65-fold in IP-selected sublines, was the type I transmembrane protein AMIGO2. As the role of AMIGO2 in ovarian cancer metastasis remains unexplored, CRISPR/Cas9 was used to reduce AMIGO2 expression, followed by in vitro and in vivo functional analyses. Knockdown of AMIGO2 modified the sphere-forming potential of ovarian cancer cells, reduced adhesion and invasion in vitro, and significantly attenuated IP metastasis. These data highlight AMIGO2 as a new target for a novel anti-metastatic therapeutic approach aimed at blocking cohesion, survival, and adhesion of metastatic tumorspheres. Highlights: Most women with ovarian cancer are diagnosed with diffuse intra-peritoneal (IP) metastases and succumb to metastatic burden. Ovarian cancer cells selected in vivo for IP metastatic aggressiveness display altered gene expression. The adhesion molecule AMIGO2 is upregulated in IP metastatic sublines and modulates ovarian cancer tumorsphere compaction. AMIGO2 represents a novel anti-metastatic target in ovarian cancer.