VDR signaling inhibits cancer-associated-fibroblasts’ release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells

Kong, Fanyang; Li, Lei; Wang, Guokun; Li, Zhao‐Shen; Kong, Xiangyu

doi:10.1136/gutjnl-2018-316627

Cited by 41 publications

(27 citation statements)

References 5 publications

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“…There is also evidence for negative cross‐talks between the two cells. This is possibly due to the expression of receptors like vitamin D receptor in CAFs . Despite this duality of functioning, the existing data is more supportive for tumorigenic interactions between the two cells.…”

Section: Positive Interactionsmentioning

confidence: 99%

Cancer‐associated fibroblasts: Secretions, interactions, and therapy

Farhood

Najafi

Mortezaee

2018

J of Cellular Biochemistry

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Tumor microenvironment (TME) could impose a great challenge for cancer targeted therapies. Immunosuppression within the TME creates a barrier between cancer cells and therapeutic approaches. A number of cells are hosted within this milieu, among them cancer-associated fibroblasts (CAFs) are the most abundant cell populations playing major roles in mediating an immunosuppressive TME. CAFs have cross-talks with almost all cells within the TME for reprogramming them into being tumorigenic. This reprogramming reduces the pre-existing tumor immunity and dampens the efficacy of chemotherapeutic approaches. CAFs would do this through releasing a myriad of factors to the TME making it an appropriate nest for tumor growth. The cells degrade and deposit extracellular matrix components, both of which are tumorigenic. Therefore, disruption of cross-talks between CAFs with other cells within the TME would be a promising approach in cancer targeted therapies.This approach is applicable through dampening dominant signals mediated by CAFs. Another interesting approach would be reprogramming of CAFs toward their normal counterpart. This would need identification of different subtypes for these cells and their functions. More knowledge is also required about selective markers for each CAF subtype. K E Y W O R D Scancer, cancer-associated fibroblasts, extracellular matrix, therapy, transforming growth factor-β, tumor microenvironment J Cell Biochem. 2019;120:2791-2800.wileyonlinelibrary.com/journal/jcb

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Section: Positive Interactionsmentioning

confidence: 99%

Cancer‐associated fibroblasts: Secretions, interactions, and therapy

Farhood

Najafi

Mortezaee

2018

J of Cellular Biochemistry

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“…Accumulating studies have indicated that aberrant genes play important roles in the initiation, progression, and prognosis of tumors and have been explored as cancer biomarkers in past decades [7][8][9][10][11][12]. Although these aberrant gene have been utilized to establish predictive models for PC prognosis prediction, no consensus on their effectiveness has yet been reached.…”

Section: Introductionmentioning

confidence: 99%

Five gene signatures were identified in the prediction of overall survival in resectable pancreatic cancer

Tian

2020

BMC Surg

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Background Although genes have been previously detected in pancreatic cancer (PC), aberrant genes that play roles in resectable pancreatic cancer should be further assessed. Methods Messenger RNA samples and clinicopathological data corrected with PC were downloaded from The Cancer Genome Atlas (TCGA). Resectable PC patients were randomly divided into a primary set and a validation set. Univariable Cox regression analysis, lasso-penalized Cox regression analysis, and multivariable Cox analysis were implemented to distinguish survival-related genes (SRGs). A risk score based on the SRGs was calculated by univariable Cox regression analysis. A genomic-clinical nomogram was established by integrating the risk score and clinicopathological data to predict overall survival (OS) in resectable PC. Results Five survival-related genes (AADAC, DEF8, HIST1H1C, MET, and CHFR) were significantly correlated with OS in resectable PC. The resectable PC patients, based on risk score, were sorted into a high-risk group that showed considerably unfavorable OS (p < 0.001) than the low-risk group, in both the primary set and the validation set. The concordance index (C-index) was calculated to evaluate the predictive performance of the nomogram were respectively in the primary set [0.696 (0.608–0.784)] and the validation set [0.682 (0.606–0.758)]. Additionally, gene set enrichment Analysis discovered several meaningful enriched pathways. Conclusion Our study identified five prognostic gene biomarkers for OS prediction and which facilitate postoperative molecular target therapy for the resectable PC, especially the nomic-clinical nomogram which may be used as an effective model for the postoperative OS evaluation and also an optimal therapeutic tool for the resectable PC.

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“…Moreover, the expression levels of miRNA-10a-5p were identified to be bountiful in CAF-derived exosomes ( Figure 1 and Table 1). Other miRNAs, such as miRNA-92ab-3p, were also copiously detected in exosomes in addition to miRNA-10a-5p [64]. In that study, it was also pointed out that the treatment of CAFs with calcitriol, an active type of Vitamin D, induces vitamin D receptor (VDR)-mediated signaling and remarkably downregulates miRNA-10a-5p levels in exosomes as well as exosome-receiving cancer cells [64].…”

Section: Mirna-10a-5pmentioning

confidence: 92%

Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication

et al. 2020

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Pancreatic cancer is malignant and the seventh leading cause of cancer-related deaths worldwide. However, chemotherapy and radiotherapy are—at most—moderately effective, indicating the need for new and different kinds of therapies to manage this disease. It has been proposed that the biologic properties of pancreatic cancer cells are finely tuned by the dynamic microenvironment, which includes extracellular matrix, cancer-associated cells, and diverse immune cells. Accumulating evidence has demonstrated that extracellular vesicles (EVs) play an essential role in communication between heterogeneous subpopulations of cells by transmitting multiplex biomolecules. EV-mediated cell–cell communication ultimately contributes to several aspects of pancreatic cancer, such as growth, angiogenesis, metastasis and therapeutic resistance. In this review, we discuss the role of extracellular vesicles and their cargo molecules in pancreatic cancer. We also present the feasibility of the inhibition of extracellular biosynthesis and their itinerary (release and uptake) for a new attractive therapeutic strategy against pancreatic cancer.

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VDR signaling inhibits cancer-associated-fibroblasts’ release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells

Cited by 41 publications

References 5 publications

Cancer‐associated fibroblasts: Secretions, interactions, and therapy

Cancer‐associated fibroblasts: Secretions, interactions, and therapy

Five gene signatures were identified in the prediction of overall survival in resectable pancreatic cancer

Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication

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