Fibrosis and cancer: A strained relationship

• Published in: Biochimica et biophysica acta. Reviews on cancer 2020-04, Vol.1873 (2), p.188356-188356, Article 188356
• Main Authors: Piersma, Bram, Hayward, Mary-Kate, Weaver, Valerie M.
• Format: Article
• Language: English
• Subjects: 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; CAF; Cancer; 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; ECM; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - immunology; Extracellular Matrix - immunology; Extracellular Matrix - pathology; Female; Fibrosis; Humans; Mechanoreciprocity; 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
• ISSN: 0304-419X; 1879-2561
• DOI: 10.1016/j.bbcan.2020.188356

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.