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

• Published in: Nature communications Vol. 11; no. 1; pp. 3546 - 16
• Main Authors: Au-Yeung, Chi-Lam, Yeung, Tsz-Lun, Achreja, Abhinav, Zhao, Hongyun, Yip, Kay-Pong, Kwan, Suet-Ying, Onstad, Michaela, Sheng, Jianting, Zhu, Ying, Baluya, Dodge L, Co, Ngai-Na, Rynne-Vidal, Angela, Schmandt, Rosemarie, Anderson, Matthew L, Lu, Karen H, Wong, Stephen T C, Nagrath, Deepak, Mok, Samuel C
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 15.07.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Cancer; Carcinoma, Ovarian Epithelial - blood; Carcinoma, Ovarian Epithelial - mortality; Carcinoma, Ovarian Epithelial - secondary; Carcinoma, Ovarian Epithelial - therapy; Cell Line, Tumor - transplantation; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic - metabolism; Cytokines - administration & dosage; Cytokines - blood; Cytokines - metabolism; Disease Models, Animal; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins - administration & dosage; GPI-Linked Proteins - blood; GPI-Linked Proteins - metabolism; Growth rate; Health risk assessment; Humans; Invasiveness; Lactoferrin - metabolism; Lectins - administration & dosage; Lectins - blood; Lectins - metabolism; Matrix Metalloproteinase 1 - metabolism; Metabolism; Metastases; Mice; Neoplasm Invasiveness - pathology; Omentum; Omentum - pathology; Ovarian cancer; Ovarian Neoplasms - blood; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Ovary; Peritoneal Neoplasms - secondary; Recombinant Proteins - administration & dosage; Survival Rate; Tumor Microenvironment; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17383-2

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.