The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

Shoucair, Issraa; Mello, Fernanda Weber; Jabalee, James; Maleki, Saeideh; Garnis, Cathie

doi:10.3390/ijms21186837

Cited by 57 publications

(59 citation statements)

References 173 publications

(312 reference statements)

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“…It is noteworthy that protein transfer via EVs from CAFs to cancer cells has not been largely addressed, since the majority of the studies focused on the role of EV-mediated transfer of miRNAs within the TME (Shoucair et al 2020). Notably, we show that the conversion of normal fibroblasts into their activated counterparts, upon stimulation with cytokines in the tumor conditioned media from cancer cells, causes the upregulation of Gal-1 expression levels, both in their intracellular compartment and in their secreted MVs (Fig.…”

Section: Discussionmentioning

confidence: 99%

Activated fibroblasts enhance cancer cell migration by microvesicles-mediated transfer of Galectin-1

Toti

Santi

Pardella

et al. 2021

J. Cell Commun. Signal.

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Cancer-associated fibroblasts (CAFs) are one of the main components of the stromal compartment in the tumor microenvironment (TME) and the crosstalk between CAFs and cancer cells is essential for tumor progression and aggressiveness. Cancer cells mediate an activation process, converting normal fibroblasts into CAFs, that are characterized by modified expression of many proteins and increased production and release of microvesicles (MVs), extracellular vesicles generated by outwards budding from the cell membrane. Recent evidence underlined that the uptake of CAF-derived MVs changes the overall protein content of tumor cells. In this paper, we demonstrate that tumor activated fibroblasts overexpress Galectin-1 (Gal-1) and consequently release MVs containing increased levels of this protein. The uptake of Gal-1 enriched MVs by tumor cells leads to the upregulation of its intracellular concentration, that strongly affects cancer cell migration, while neither proliferation nor adhesion are altered. Accordingly, tumor cells co-cultured with fibroblasts silenced for Gal-1 have a reduced migratory ability. The present work reveals the key role of an exogenous protein, Gal-1, derived from activated fibroblasts, in cancer progression, and contributes to clarify the importance of MVs-mediated protein trafficking in regulating tumor-stroma crosstalk.

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Section: Discussionmentioning

confidence: 99%

Activated fibroblasts enhance cancer cell migration by microvesicles-mediated transfer of Galectin-1

Toti

Santi

Pardella

et al. 2021

J. Cell Commun. Signal.

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“…The origin of CAFs is still poorly understood and it has been suggested that tumour cells can promote the transformation of normal fibroblasts into CAFs through EV-associated miRNAs [ 69 ]. For example, in HCC, high-metastatic cells have been shown to secrete exosomal miR-1247-3p, which in turn was demonstrated to be taken up by fibroblasts resulting in their activation, and the resultant CAFs secreted proinflammatory cytokines and promoted tumour stemness, EMT, chemoresistance and lung metastasis [ 70 ].…”

Section: Mirnas In Intercellular Communication In the Tmementioning

confidence: 99%

MicroRNAs in Metastasis and the Tumour Microenvironment

Solé

Lawrie

2021

IJMS

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Metastasis is the process whereby cancer cells migrate from the primary tumour site to colonise the surrounding or distant tissue or organ. Metastasis is the primary cause of cancer-related mortality and approximately half of all cancer patients present at diagnosis with some form of metastasis. Consequently, there is a clear need to better understand metastasis in order to develop new tools to combat this process. MicroRNAs (miRNAs) regulate gene expression and play an important role in cancer development and progression including in the metastatic process. Particularly important are the roles that miRNAs play in the interaction between tumour cells and non-tumoral cells of the tumour microenvironment (TME), a process mediated largely by circulating miRNAs contained primarily in extracellular vesicles (EVs). In this review, we outline the accumulating evidence for the importance of miRNAs in the communication between tumour cells and the cells of the TME in the context of the pre-metastatic and metastatic niche.

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“…CAFs display distinct morphological and biological characteristics from normal fibroblasts. From the molecular point of view, they express high levels of α-smooth muscle actin (α-SMA), fibroblast activation protein (FAP), fibroblast-specific protein-1 (FSP-1), platelet-derived growth factor receptor α/β (PDGFR α/β) and vimentin [ 22 ].CAFs promote UADT SCC progression by secreting cytokines/growth factors and ECM proteins, as well as MMPs, thus influencing tumor cell proliferation, angiogenesis, inflammation, metastatic invasion, and drug resistance [ 103 , 104 , 105 , 106 ].…”

Section: Ecm In Uadt Scc: An Intertwined Storymentioning

confidence: 99%

ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers

Fejza

Camicia

Poletto

et al. 2021

Cancers

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Squamous cell carcinomas (SCC) include a number of different types of tumors developing in the skin, in hollow organs, as well as the upper aerodigestive tract (UADT) including the head and neck region and the esophagus which will be dealt with in this review. These tumors are often refractory to current therapeutic approaches with poor patient outcome. The most important prognostic determinant of SCC tumors is the presence of distant metastasis, significantly correlating with low patient survival rates. Rapidly emerging evidence indicate that the extracellular matrix (ECM) composition and remodeling profoundly affect SSC metastatic dissemination. In this review, we will summarize the current knowledge on the role of ECM and its remodeling enzymes in affecting the growth and dissemination of UADT SCC. Taken together, these published evidence suggest that a thorough analysis of the ECM composition in the UADT SCC microenvironment may help disclosing the mechanism of resistance to the treatments and help defining possible targets for clinical intervention.

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The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

Cited by 57 publications

References 173 publications

Activated fibroblasts enhance cancer cell migration by microvesicles-mediated transfer of Galectin-1

Activated fibroblasts enhance cancer cell migration by microvesicles-mediated transfer of Galectin-1

MicroRNAs in Metastasis and the Tumour Microenvironment

ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers

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