In vivo selection of highly metastatic human ovarian cancer sublines reveals role for AMIGO2 in intra-peritoneal metastatic regulation

Yueying Liu, Jing Yang, Zonggao Shi, Xuejuan Tan, Norman Jin, Catlin O'Brien, Connor Ott, Anna Grisoli, Eric Lee, Kelly Volk, Meghan Conroy, Emily Franz, Annamarie Bryant, Leigh Campbell, Brian Crowley, Stephen Grisoli, Aris T. Alexandrou, Chunyan Li, Elizabeth I. Harper, Marwa AsemJeff Johnson, Annemarie Leonard, Katie Santanello, Ashley Klein, Qingfei Wang, Siyuan Zhang, Tyvette S. Hilliard, M. Sharon Stack

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)163-173
Number of pages11
JournalCancer Letters
Volume503
DOIs
StatePublished - Apr 10 2021
Externally publishedYes

Keywords

  • AMIGO2
  • Intra-peritoneal metastasis
  • Invasion]
  • Multi-cellular aggregate
  • Ovarian cancer
  • Spheroid
  • Tumorsphere [deleted adhesion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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