Fibrosis and cancer: A strained relationship

Bram Piersma; Mary-Kate Hayward; Valerie M Weaver

doi:10.1016/j.bbcan.2020.188356

Fibrosis and cancer: A strained relationship

Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188356. doi: 10.1016/j.bbcan.2020.188356. Epub 2020 Mar 5.

Authors

Bram Piersma¹, Mary-Kate Hayward², Valerie M Weaver³

Affiliations

¹ Department 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.
² Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco (UCSF), USA.
³ Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco (UCSF), USA; Departments of Radiation Oncology, Bioengineering and Therapeutic Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, UCSF Helen Diller Comprehensive Cancer Center, 513 Parnassus Avenue, HSE565, San Francisco, CA 94143-0456, USA. Electronic address: [email protected].

Abstract

Tumors are characterized by extracellular matrix (ECM) deposition, remodeling, and cross-linking that drive fibrosis to stiffen the stroma and promote malignancy. The stiffened stroma enhances tumor cell growth, survival and migration and drives a mesenchymal transition. A stiff ECM also induces angiogenesis, hypoxia and compromises anti-tumor immunity. Not surprisingly, tumor aggression and poor patient prognosis correlate with degree of tissue fibrosis and level of stromal stiffness. In this review, we discuss the reciprocal interplay between tumor cells, cancer associated fibroblasts (CAF), immune cells and ECM stiffness in malignant transformation and cancer aggression. We discuss CAF heterogeneity and describe its impact on tumor development and aggression focusing on the role of CAFs in engineering the fibrotic tumor stroma and tuning tumor cell tension and modulating the immune response. To illustrate the role of mechanoreciprocity in tumor evolution we summarize data from breast cancer and pancreatic ductal carcinoma (PDAC) studies, and finish by discussing emerging anti-fibrotic strategies aimed at treating cancer.

Keywords: CAF; Cancer; ECM; Fibrosis; Mechanoreciprocity.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Breast / pathology
Breast Neoplasms / drug therapy
Breast Neoplasms / immunology
Breast Neoplasms / mortality
Breast Neoplasms / pathology*
Cancer-Associated Fibroblasts / drug effects
Cancer-Associated Fibroblasts / immunology
Cancer-Associated Fibroblasts / pathology*
Carcinoma, Pancreatic Ductal / drug therapy
Carcinoma, Pancreatic Ductal / immunology
Carcinoma, Pancreatic Ductal / mortality
Carcinoma, Pancreatic Ductal / pathology*
Cell Transformation, Neoplastic / drug effects
Cell Transformation, Neoplastic / immunology
Cell Transformation, Neoplastic / pathology
Clinical Trials as Topic
Epithelial-Mesenchymal Transition / drug effects
Epithelial-Mesenchymal Transition / immunology
Extracellular Matrix / immunology
Extracellular Matrix / pathology
Female
Fibrosis
Humans
Pancreas / pathology
Pancreatic Neoplasms / drug therapy
Pancreatic Neoplasms / immunology
Pancreatic Neoplasms / mortality
Pancreatic Neoplasms / pathology*
Prognosis
Progression-Free Survival
Treatment Outcome
Tumor Escape / drug effects
Tumor Microenvironment / drug effects
Tumor Microenvironment / immunology

Abstract

Publication types

MeSH terms

Grants and funding