Collagens in Cancer: Structural Regulators and Guardians of Cancer Progression

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Abstract

Collagen is one of the most abundant proteins in animals and a major component of the extracellular matrix (ECM) in tissues. Besides playing a role as a structural building block of tissues, collagens can modulate the behavior of cells, and their deregulation can promote diseases such as cancer. In tumors, collagens and many other ECM molecules are mainly produced by fibroblasts, and recent evidence points toward a role of tumor-derived collagens in tumor progression and metastasis. In this review, we focus on the newly discovered functions of collagens in cancer. Novel findings have revealed the role of collagens in tumor dormancy and immune evasion, as well as their interplay with cancer cell metabolism. Collagens could serve as prognostic markers for patients with cancer, and therapeutic strategies targeting the collagen ECM have the potential to prevent tumor progression and metastasis.

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Most cited references 83

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Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice

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Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Sustained inflammation induced the formation of neutrophil extracellular traps (NETs), and these were required for awakening dormant cancer. Mechanistic analysis revealed that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin α3β1 signaling. Antibodies against NET-remodeled laminin prevented awakening of dormant cells. Therapies aimed at preventing dormant cell awakening could potentially prolong the survival of cancer patients.

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Author and article information

Contributors

Daniela De Martino: (View ORCID Profile)

Jose Javier Bravo-Cordero: (View ORCID Profile)

Journal

Title: Cancer Research

Publisher: American Association for Cancer Research (AACR)

ISSN (Print): 0008-5472

ISSN (Electronic): 1538-7445

Publication date Created: May 02 2023

Publication date Created: January 13 2023

Publication date (Print): May 02 2023

Publication date (Electronic): January 13 2023

Volume: 83

Issue: 9

Pages: 1386-1392

Article

DOI: 10.1158/0008-5472.CAN-22-2034

PubMed ID: 36638361

SO-VID: 1488b24c-5dec-4b17-a443-81fdabfe4ff9

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