Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Linares, Jenniffer; Marín-Jiménez, Juan A.; Badia-Ramentol, Jordi; Calon, Alexandre

doi:10.3389/fcell.2020.621070

Cited by 65 publications

(62 citation statements)

References 235 publications

(248 reference statements)

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“…One example is the multifunctional cytokine TGF-β that, in physiological conditions, regulates different mechanisms, such as morphogenesis, development, wound healing, and others, while, if deregulated, can promote aggressive phenotypes in cancers. Once activated, CAFs can secrete various messengers that can promote invasion and metastasis [ 69 ]. Some of these factors enhance EMT or ECM remodeling, as discussed in previous paragraphs.…”

Section: Caf–tumor Communicationmentioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Asif

Longobardi

Hahne

et al. 2021

Cancers

142

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Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.

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Section: Caf–tumor Communicationmentioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Asif

Longobardi

Hahne

et al. 2021

Cancers

142

View full text Add to dashboard Cite

show abstract

“…On the other hand, radiotherapy was proposed to increase paracrine signaling between fibroblasts and tumor cells via insulin-like growth factor (IGF) and TGF-b pathways (291,292). Chemotherapy can also modulate the tumor microenvironment (293). CAF derived growth arrest-specific protein 6, which is a ligand of TAM receptors, was reported to increase during cisplatin based chemotherapy (294).…”

Section: Recruitment and Polarization Of Tams By Cafsmentioning

confidence: 99%

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Günaydın

2021

Front. Oncol.

121

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Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) are among the most important and abundant players of the tumor microenvironment. CAFs as well as TAMs are known to play pivotal supportive roles in tumor growth and progression. The number of CAF or TAM cells is mostly correlated with poor prognosis. Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are also involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. Here, the current understanding of the distinct mechanisms about the complex interplay between CAFs and TAMs are summarized. In addition, the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion are highlighted, focusing on the synergistic pleiotropic effects. CAFs and TAMs are crucial components of the tumor microenvironment; thus, they may prove to be potential therapeutic targets. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis.

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“…In fact, the induction of the cyclooxygenase-2 (COX-2)/prostaglandin E2 cascade induced by HP infection leads to the hypermethylation of miR-149 in CAFs, eventually resulting in increased IL-6 secretion [94]. Based on these premises and given the role played by IL-6 in inducing EMT through the JAK2/STAT3 pathway, recent studies have investigated the role of neutralizing antibodies, including AG490 [95,96]. A study conducted by Wu and colleagues has suggested that the simultaneous inhibition of JAK2/STAT3 and IL-6 using AG490 might impair tumor diffusion induced by CAFs to the peritoneum; as such, IL-6-targeted therapies could represent a complementary treatment approach due to their action on fibroblasts [97].…”

Section: Cancer-associated Fibroblastsmentioning

confidence: 99%

Tumor-Associated Macrophages and Inflammatory Microenvironment in Gastric Cancer: Novel Translational Implications

Rihawi

Ricci

Rizzo

et al. 2021

IJMS

114

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Gastric cancer (GC) represents the fifth most frequently diagnosed cancer worldwide, with a poor prognosis in patients with advanced disease despite many improvements in systemic treatments in the last decade. In fact, GC has shown resistance to several treatment options, and thus, notable efforts have been focused on the research and identification of novel therapeutic targets in this setting. The tumor microenvironment (TME) has emerged as a potential therapeutic target in several malignancies including GC, due to its pivotal role in cancer progression and drug resistance. Therefore, several agents and therapeutic strategies targeting the TME are currently under assessment in both preclinical and clinical studies. The present study provides an overview of available evidence of the inflammatory TME in GC, highlighting different types of tumor-associated cells and implications for future therapeutic strategies.

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Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy

Cited by 65 publications

References 235 publications

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Tumor-Associated Macrophages and Inflammatory Microenvironment in Gastric Cancer: Novel Translational Implications

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