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.
Highlights
Cancer-associated fibroblasts (CAFs) are contributing to the production of a wide variety of secreted factors impacting tumor progression by directly regulating malignant cancer cells aggressiveness or by indirectly reprogramming tumor immunity and angiogenesis (Sahai et al, 2020)
CXC ligand (CXCL)-1 and CXCL-8 positivity in CAFs was significantly associated with poor prognosis in gastric cancer patients (Naito et al, 2019), whereas CXCL-8,−10, and−11 CAFs expression correlated with resistance to neoadjuvant CT and poor prognosis in breast cancer (BC) (Xu et al, 2020)
Since CAFs complete depletion or blockade of fibroblastrich tumor stroma formation resulted in decreased antitumor immune infiltration and more aggressive tumors, recent strategies have rather focused on the regulation of CAFs originating paracrine and autocrine signaling (Özdemir et al, 2014; Rhim et al, 2014)
Summary
Cancer-associated fibroblasts (CAFs) are contributing to the production of a wide variety of secreted factors impacting tumor progression by directly regulating malignant cancer cells aggressiveness or by indirectly reprogramming tumor immunity and angiogenesis (Sahai et al, 2020). It is widely accepted that the functional phenotype of CAFs is in part determined by the cell of origin, including but not restricted to local resident fibroblasts (D’Arcangelo et al, 2020; Sahai et al, 2020). Whether CAFs functional heterogeneity is maintained among different solid tumor types or is a constant evolutionary state is still a debated question. Recent studies have been investigating the determinants of CAFs secretome and their therapeutic interest across different tumor types. As a matter of fact, recent advances in the understanding of CAFs secretome determinants and functions have brought to light the multiple benefits of using CAFs-secreted factors as actionable biomarkers for cancer diagnosis, treatment, and prognosis
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