Cancer associated fibroblasts transfer lipids and proteins to cancer cells through cargo vesicles supporting tumor growth

Santi, Alice; Caselli, Anna; Ranaldi, Francesco; Paoli, Paolo; Mugnaioni, Camilla; Michelucci, Elena; Cirri, Paolo

doi:10.1016/j.bbamcr.2015.09.013

Cited by 84 publications

(84 citation statements)

References 36 publications

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“…In the present study, we employed a sequential centrifugation method to isolate MVs. Consistent with previous studies, MVs with diameters ranging from 100 to 600 nm were collected from various cancer cells (10,40). Because the MVs were observed to be transported to adjacent cells, our MV isolation method is appropriate for use in MV research.…”

Section: Discussionmentioning

confidence: 67%

Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer

Kang

Kim

2018

FASEB j.

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Extracellular vesicles contain various cellular components that are involved in tumor growth, metastasis, and immune escape. Extracellular vesicles are classified into 2 groups, namely, exosomes and microvesicles (MV). Although the formation and roles of exosomes have been studied, the exact functions of MVs and mechanisms underlying MV release are not fully understood. We found that epidermal growth factor accelerates the release of MVs from the plasma membrane by inducing NF‐κB activation and CD133 expression. The amount and sizes of budding MVs were found to be dependent on the expression level of CD133, which regulates the activities of the small guanosine 5′‐triphosphatases RhoA and Rac1. CD133‐containing MVs released from KRAS mutant colon cancer cells delivered KRAS mutant to adjacent nontumorigenic cells and activated KRAS downstream signaling. CD133‐containing MVs were found to promote the migration and invasion of adjacent cells. CD133‐containing MVs induced the development of chemoresistance by abolishing the inhibitory effects of anti‐epidermal growth factor receptor (EGFR) drugs on cell proliferation and motility in colon cancer. These results suggest that CD133 acts as a novel modulator in MV release and in oncoprotein trafficking. CD133 can serve as a therapeutic target for treatment of anti‐EGFR drug‐resistant colon cancer.—Kang, M., Kim, S., Ko, J. Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer. FASEB J. 33, 4248–4260 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 67%

Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer

Kang

Kim

2018

FASEB j.

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“…However, recent studies revealed that fibroblasts, through exosome secretion, potentiate breast cancer cells and therapy resistance (34,35). Santi et al showed that CAFs transfer lipid and proteins to prostate and melanoma cancer cells through cargo vesicles that support tumor growth (36). Those studies revealed the important impact of stromal and tumor cell crosstalk through EV trafficking on tumor development; however, they did not evaluate the impact of the CAF environment.…”

Section: Anxa6 Lrp1 and Tsp1 Expression In Pda Is Mainly Driven Bymentioning

confidence: 96%

Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness

Leca¹,

Martinez²,

Lac³

et al. 2016

Journal of Clinical Investigation

184

160

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“…ANXA6+ (Annexin 6/LDL receptor-related protein-1/thrombospondin-1 complex) CAFs-secreted EVs enhanced tumor cell aggressiveness in pancreatic cancer (Leca et al, 2016). Fibroblast-derived exosomes induced mobilization, invasion (Luga et al, 2012), resistance to therapy and tumor recurrence in breast cancer (Boelens et al, 2014), while CAFs EVs-mediated transfer of proteins and lipids enhanced cancer proliferation rate of human prostate cancer and melanoma cell lines (Santi et al, 2015). The EVs transfer of surface receptors or intracellular material has been also associated with immunosuppressive and tumor-promoting functions.…”

Section: New Horizons Of Organoids Application: Modeling Evs Releasementioning

confidence: 99%

Modeling Cell Communication in Cancer With Organoids: Making the Complex Simple

Fiorini

Veghini

Corbo

2020

Front. Cell Dev. Biol.

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Homotypic and heterotypic interactions between cells are of crucial importance in multicellular organisms for the maintenance of physiological functions. Accordingly, changes in cell-to-cell communication contribute significantly to tumor development. Cancer cells engage the different components of the tumor microenvironment (TME) to support malignant proliferation, escape immune control, and favor metastatic spreading. The interaction between cancerous and non-cancerous cell types within tumors occurs in many ways, including physical contact and paracrine signaling. Furthermore, local and long-range transfer of biologically active molecules (e.g., DNA, RNA, and proteins) can be mediated by small extracellular vesicles (EVs) and this has been shown to influence many aspects of tumor progression. As it stands, there is a critical need for suitable experimental systems that enable modeling the cell-to-cell communications occurring in cancer. Given their intrinsic complexity, animal models represent the ideal system to study cell-to-cell interaction between different cell types; however, they might make difficult to assess individual contribution to a given phenotype. On the other hand, simplest experimental models (i.e., in vitro culture systems) might be of great use when weighing individual contributions to a given phenomenon, yet it is imperative that they share a considerable number of features with human cancer. Of the many culture systems available to the scientific community, patient-derived organoids already proved to faithfully recapitulate many of the traits of patients' disease, including genetic heterogeneity and response to therapy. The organoid technology offers several advantages over conventional monolayer cell cultures, including the preservation of the topology of cell-to-cell and cell-to-matrix interactions as observed in vivo. Several studies have shown that organoid cultures can be successfully used to study interaction between cancer cells and cellular components of the TME. Here, we discuss the potential of using organoids to model the interplay between cancer and non-cancer cells in order to unveil biological mechanisms involved in cancers initiation and progression, which might ultimately lead to the identification of novel intervention strategy for those diseases.

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Cancer associated fibroblasts transfer lipids and proteins to cancer cells through cargo vesicles supporting tumor growth

Cited by 84 publications

References 36 publications

Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer

Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer

Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness

Modeling Cell Communication in Cancer With Organoids: Making the Complex Simple

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