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.

Advanced ovarian cancer usually spreads to the omentum. Here, the authors show that circulating intelectin-1 (ITLN1) has prognostic significance in patients with advanced ovarian cancer, and that mesothelial cell-derived ITLN1 in the omental tumor microenvironment suppresses ovarian cancer progression.

Details

Title
ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment
Author
Chi-Lam, Au-Yeung 1 ; Yeung Tsz-Lun 1 ; Achreja Abhinav 2   VIAFID ORCID Logo  ; Zhao Hongyun 2 ; Kay-Pong, Yip 3 ; Suet-Ying, Kwan 4 ; Onstad Michaela 4 ; Sheng Jianting 5 ; Zhu, Ying 5 ; Baluya Dodge L 6 ; Ngai-Na, Co 4 ; Rynne-Vidal, Angela 4   VIAFID ORCID Logo  ; Schmandt Rosemarie 1 ; Anderson, Matthew L 7   VIAFID ORCID Logo  ; Lu, Karen H 1 ; Wong, Stephen T, C 5 ; Nagrath Deepak 2   VIAFID ORCID Logo  ; Mok, Samuel C 1   VIAFID ORCID Logo 

1  The University of Texas MD Anderson Cancer Center, Department of Gynecologic Oncology and Reproductive Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
2  University of Michigan, Department of Biomedical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
3  University of South Florida, Department of Molecular Pharmacology and Physiology, Tampa, USA (GRID:grid.170693.a) (ISNI:0000 0001 2353 285X) 
4  The University of Texas MD Anderson Cancer Center, Department of Gynecologic Oncology and Reproductive Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
5  Houston Methodist Research Institute, Weill Cornell Medicine, Department of Systems Medicine and Bioengineering, Houston, USA (GRID:grid.63368.38) (ISNI:0000 0004 0445 0041); Center for Precision Oncology, Houston Methodist Cancer Center, Houston, USA (GRID:grid.63368.38) (ISNI:0000 0004 0445 0041) 
6  The University of Texas MD Anderson Cancer Center, Department of Diagnostic Imaging-Interventional Radiology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
7  Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Department of Obstetrics and Gynecology, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-17383-2
ProQuest document ID
2423961938
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.