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A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
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Fibrosis and cancer: A strained relationship
Bram Piersma1, Mary-Kate Hayward2, Valerie M Weaver3
1Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco (UCSF), USA; Matrix research group, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, the Netherlands.
Biochimica Et Biophysica Acta. Reviews on Cancer
|March 10, 2020
Summary
Tumor fibrosis stiffens the extracellular matrix (ECM), promoting cancer growth and spread. Targeting this fibrosis offers a new strategy to combat aggressive cancers.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Biology
Background:
- Tumors develop through extracellular matrix (ECM) deposition, remodeling, and cross-linking, leading to fibrosis and stromal stiffening.
- This stiffened tumor stroma enhances cancer cell growth, survival, migration, and mesenchymal transition, while also promoting angiogenesis, hypoxia, and immune suppression.
- Increased tissue fibrosis and stromal stiffness correlate with tumor aggression and poor patient prognosis.
Purpose of the Study:
- To review the reciprocal interactions between tumor cells, cancer-associated fibroblasts (CAFs), immune cells, and ECM stiffness in cancer development and progression.
- To explore CAF heterogeneity and its role in fibrotic stroma engineering, tumor cell mechanotransduction, and immune modulation.
- To discuss emerging anti-fibrotic therapies for cancer treatment.
Main Methods:
- Literature review focusing on the interplay between cancer cells, CAFs, immune cells, and ECM stiffness.
- Analysis of data from breast cancer and pancreatic ductal carcinoma (PDAC) studies to illustrate mechanoreciprocity in tumor evolution.
- Discussion of emerging anti-fibrotic strategies.
Main Results:
- Fibrosis and stromal stiffness are key drivers of tumor malignancy, enhancing tumor cell proliferation, survival, migration, and immune evasion.
- Cancer-associated fibroblasts (CAFs) play a critical role in engineering the fibrotic tumor microenvironment, influencing tumor cell mechanics and immune responses.
- Mechanoreciprocity between tumor cells and the ECM is central to tumor evolution, as evidenced in breast cancer and PDAC.
Conclusions:
- Stromal stiffness and fibrosis are critical determinants of cancer aggression and patient outcomes.
- Targeting the interplay between CAFs, ECM, and tumor cells, particularly through anti-fibrotic strategies, holds promise for novel cancer therapies.
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