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Updated: Sep 29, 2025

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

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Cancer-Associated Fibroblasts Regulate Kinase Activity in Mesothelioma Cell Lines via Paracrine Signaling and Thereby

Alexander Mathilakathu1, Michael Wessolly1, Elena Mairinger1

  • 1Institute of Pathology, University Hospital Essen, University of Duisburg Essen, 45147 Essen, Germany.

International Journal of Molecular Sciences
|March 25, 2022
PubMed
Abstract

Insights

Cancer-associated fibroblasts (CAFs) significantly alter malignant pleural mesothelioma (MPM) cell signaling. Targeting the MAPK pathway with MEK or ERK inhibitors shows promise for improving MPM treatment outcomes.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Signaling

Background:

  • Malignant pleural mesothelioma (MPM) exhibits poor prognosis due to treatment resistance.
  • MPM cells manipulate the immune microenvironment, involving cytokines like TGF-ß and fibrocytes.
  • Interactions between cancer cells and cancer-associated fibroblasts (CAFs) are crucial for tumor progression.

Purpose of the Study:

  • To investigate the role of CAFs in MPM progression.
  • To analyze the impact of cancer cell-fibroblast interactions on kinase signaling in vitro.

Main Methods:

  • Paracrine signaling simulated in vitro using MPM cell lines and fibroblast-conditioned medium (CM).
  • Analyzed proliferation, migration, apoptosis, necrosis, and viability.
  • Kinase activity assessed using the PamStation12 platform.

Main Results:

  • Myofibroblast-derived CM induced significant phosphorylation changes in MPM cell lines.
  • Effects varied between MPM subtypes and fibroblast origins, with IMR-90 CM showing a stronger impact.
  • Phosphorylation changes primarily affected the MAPK signaling pathway.

Conclusions:

  • Secreted factors from myofibroblasts significantly influence kinase phosphorylation, particularly the MAPK pathway in MPM cells.
  • MEK or ERK inhibitors show potential therapeutic effects for MPM.
  • Combination therapy with MEK/ERK inhibitors and cisplatin may improve clinical outcomes for MPM patients.
Keywords:
MAPK signalingMEK and ERK inhibitorscancer-associated fibroblastskinasesmicroenvironmentphosphorylationpleural mesothelioma

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