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Updated: Jul 17, 2025

A Biomimetic Model for Liver Cancer to Study Tumor-Stroma Interactions in a 3D Environment with Tunable Bio-Physical Properties
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The extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability

Arya Mariam Roy1, Renuka Iyer1, Sayan Chakraborty2

  • 1Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Cell Reports. Medicine
|August 31, 2023
PubMed

Insights

Disorganized extracellular matrix (ECM) in hepatocellular carcinoma (HCC) affects cancer cell behavior and treatment response. Understanding ECM roles may reveal new therapeutic targets for HCC.

Area of Science:

  • Oncology
  • Biochemistry
  • Cell Biology

Background:

  • The tumor microenvironment (TME) is shaped by the extracellular matrix (ECM), which influences cancer cell behavior.
  • Disorganized ECM in hepatocellular carcinoma (HCC) contributes to treatment resistance.
  • Key ECM proteins driving HCC TME and therapeutic resistance remain poorly understood.

Purpose of the Study:

  • To discuss the impact of ECM components on hepatocytes and their support network during HCC tumorigenesis.
  • To detail how ECM proteins transmit mechanical signals within the liver TME.
  • To highlight the role of ECM disorganization in responses to targeted and immune checkpoint inhibitor therapies.

Main Methods:

  • Literature review and synthesis of existing research on ECM in HCC.
  • Analysis of ECM protein contributions to hepatocyte function and TME dynamics.
  • Exploration of ECM-mediated signaling pathways and their therapeutic implications.

Main Results:

  • ECM components significantly influence hepatocyte behavior and the liver TME during tumorigenesis.
  • ECM proteins transduce mechanical signals, altering the TME's structural and signaling landscape.
  • ECM disorganization plays a critical role in the efficacy of targeted therapies and immune checkpoint inhibitors.

Conclusions:

  • A comprehensive understanding of ECM components in HCC is crucial for identifying novel therapeutic targets.
  • Targeting ECM disorganization may overcome therapeutic resistance in HCC.
  • Characterizing ECMs offers a roadmap for developing innovative strategies against HCC.
Keywords:
YAP/TAZagrinchronic liver inflammationcollagenextracellular matrixfibrosisglypican-3hepatocellular carcinomaimmunotherapymechanotransductiontargeted therapies

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