Tumor decellularization reveals proteomic and mechanical characteristics of the extracellular matrix of primary liver cancer

Gilles S van Tienderen, James Conboy, Iain Muntz, Jorke Willemse, Jantine Tieleman, Kathryn Monfils, Ivo J Schurink, Jeroen A A Demmers, Michail Doukas, Gijsje H Koenderink, Luc J W van der Laan, Monique M A Verstegen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
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Tumor initiation and progression are critically dependent on interaction of cancer cells with their cellular and extracellular microenvironment. Alterations in the composition, integrity, and mechanical properties of the extracellular matrix (ECM) dictate tumor processes including cell proliferation, migration, and invasion. Also in primary liver cancer, consisting of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the dysregulation of the extracellular environment by liver fibrosis and tumor desmoplasia is pertinent. Yet, the exact changes occurring in liver cancer ECM remain uncharacterized and underlying tumor-promoting mechanisms remain largely unknown. Herein, an integrative molecular and mechanical approach is used to extensively characterize the ECM of HCC and CCA tumors by utilizing an optimized decellularization technique. We identified a myriad of proteins in both tumor and adjacent liver tissue, uncovering distinct malignancy-related ECM signatures. The resolution of this approach unveiled additional ECM-related proteins compared to large liver cancer transcriptomic datasets. The differences in ECM protein composition resulted in divergent mechanical properties on a macro- and micro-scale that are tumor-type specific. Furthermore, the decellularized tumor ECM was employed to create a tumor-specific hydrogel that supports patient-derived tumor organoids, which provides a new avenue for personalized medicine applications. Taken together, this study contributes to a better understanding of alterations to composition, stiffness, and collagen alignment of the tumor ECM that occur during liver cancer development.

Original languageEnglish
Article number213289
JournalBiomaterials Advances
Early online date18 Jan 2023
Publication statusPublished - Mar 2023

Bibliographical note

Funding Information:
This project was partly funded by the Erasmus MC Human Disease Model Award 2018 (HDMA-380801), by the Medical Delta program grant (Regenerative Medicine 4D), by ENW-XS (Project OCENW.XS21.2.003 ) of the Dutch Research Council (NWO), by the Convergence program Syn-Cells for Health(care) under the theme of Health and Technology, and a grant from the NWO Talent Program ( VI.C.182.004 ).

Publisher Copyright:
© 2023 The Authors


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