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Review
. 2021 Jan 22:8:621070.
doi: 10.3389/fcell.2020.621070. eCollection 2020.

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Jenniffer Linares  1 , Juan A Marín-Jiménez  2 , Jordi Badia-Ramentol  1 , Alexandre Calon  1
Affiliations
Review

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Jenniffer Linares et al. Front Cell Dev Biol. .

Abstract

Multiple lines of evidence are indicating that cancer development and malignant progression are not exclusively epithelial cancer cell-autonomous processes but may also depend on crosstalk with the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are abundantly represented in the TME and are continuously interacting with cancer cells. CAFs are regulating key mechanisms during progression to metastasis and response to treatment by enhancing cancer cells survival and aggressiveness. The latest advances in CAFs biology are pointing to CAFs-secreted factors as druggable targets and companion tools for cancer diagnosis and prognosis. Especially, extensive research conducted in the recent years has underscored the potential of several cytokines as actionable biomarkers that are currently evaluated in the clinical setting. In this review, we explore the current understanding of CAFs secretome determinants and functions to discuss their clinical implication in oncology.

Keywords: cancer; cancer-associated fibroblast (CAF); growth factors; metastasis; secreted factors; secretome; therapy; tumor microenvironment (TME).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Determinants of CAFs secretome during cancer progression. Secreted factors as well as extracellular vesicle (EV)-dependent autocrine and paracrine crosstalk modulate the secretory profile of CAFs. Direct physical interaction between CAFs and epithelial cancer cells or between CAFs and components of the extracellular matrix may additionally regulate CAFs secretome.
Figure 2
Figure 2
Several CAFs subtypes have been recently described in cancers of distinct origin. CAFs heterogeneity is associated with specific markers and discrete functions. Remarkably, CAFs characteristics may be related to their spatial localization in the tumor.
Figure 3
Figure 3
Anti-cancer therapy impacts CAFs secretome. Stromal elements develop their own response to systemic chemotherapy, radiotherapy, and targeted therapy. As a result, CAFs response to treatment may diminish direct anti-cancer drug efficiency by promoting cancer cells self-renewal and survival.
Figure 4
Figure 4
CAFs secretome determines cancer progression. CAF-secreted factors regulate cancer development by enhancing directly epithelial cancer cells self-renewal and aggressiveness. Alternatively, a range of CAF-secreted factors may support progression to metastasis by maintaining an immunosuppressive environment or by enhancing pro-tumorigenic angiogenesis.
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