ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment

Chi Lam Au-Yeung, Tsz Lun Yeung, Abhinav Achreja, Hongyun Zhao, Kay Pong Yip, Suet Ying Kwan, Michaela Onstad, Jianting Sheng, Ying Zhu, Dodge L. Baluya, Ngai Na Co, Angela Rynne-Vidal, Rosemarie Schmandt, Matthew L. Anderson, Karen H. Lu, Stephen T.C. Wong, Deepak Nagrath, Samuel C. Mok

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

Original languageEnglish (US)
Article number3546
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Jul 15 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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