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Omentum-derived matrix enables the study of metastatic ovarian cancer and stromal cell functions in a physiologically relevant environment

Authors :
Lisa J. Neilson
Douglas Cartwright
Maija Risteli
Elina M. Jokinen
Lynn McGarry
Toni Sandvik
Konstantina Nikolatou
Kelly Hodge
Samuel Atkinson
Maria Vias
Emily J. Kay
James D. Brenton
Leo M. Carlin
David M. Bryant
Tuula Salo
Sara Zanivan
Source :
Matrix Biology Plus, Vol 19, Iss , Pp 100136- (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

High-grade serous (HGS) ovarian cancer is the most lethal gynaecological disease in the world and metastases is a major cause. The omentum is the preferential metastatic site in HGS ovarian cancer patients and in vitro models that recapitulate the original environment of this organ at cellular and molecular level are being developed to study basic mechanisms that underpin this disease. The tumour extracellular matrix (ECM) plays active roles in HGS ovarian cancer pathology and response to therapy. However, most of the current in vitro models use matrices of animal origin and that do not recapitulate the complexity of the tumour ECM in patients.Here, we have developed omentum gel (OmGel), a matrix made from tumour-associated omental tissue of HGS ovarian cancer patients that has unprecedented similarity to the ECM of HGS omental tumours and is simple to prepare. When used in 2D and 3D in vitro assays to assess cancer cell functions relevant to metastatic ovarian cancer, OmGel performs as well as or better than the widely use Matrigel and does not induce additional phenotypic changes to ovarian cancer cells. Surprisingly, OmGel promotes pronounced morphological changes in cancer associated fibroblasts (CAFs). These changes were associated with the upregulation of proteins that define subsets of CAFs in tumour patient samples, highlighting the importance of using clinically and physiologically relevant matrices for in vitro studies. Hence, OmGel provides a step forward to study the biology of HGS omental metastasis. Metastasis in the omentum are also typical of other cancer types, particularly gastric cancer, implying the relevance of OmGel to study the biology of other highly lethal cancers.

Details

Language :
English
ISSN :
25900285
Volume :
19
Issue :
100136-
Database :
Directory of Open Access Journals
Journal :
Matrix Biology Plus
Publication Type :
Academic Journal
Accession number :
edsdoj.4dce9ee5303495aaec66cd09d019f16
Document Type :
article
Full Text :
https://doi.org/10.1016/j.mbplus.2023.100136