PDAC-derived exosomes enrich the microenvironment in MDSCs in a <i>SMAD4</i>-dependent manner through a new calcium related axis

Basso, Daniela; Gremese, Elisa; Padoan, Andrea; Fogar, Paola; Furlanello, Sara; Aita, Ada; Bozzato, Dania; Zambon, Carlo–Federico; Arrigoni, Giorgio; Frasson, Chiara; Franchin, Cinzia; Moz, Stefania; Brefort, Thomas; Laufer, Thomas; Navaglia, Filippo; Pedrazzoli, Sergio; Basso, Giuseppe; Plebani, Mario

doi:10.18632/oncotarget.20863

Cited by 56 publications

(58 citation statements)

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“…The inconsistent results were probably due to the different tumour microenvironment(s) which act on tumour cells and affected the expression of miR‐1247‐5p. The latest studies showed that microRNAs have interaction with the tumour microenvironment via a variety of molecular pathways . Shi et al investigated the expression profile of miR‐1247‐5p in pancreatic cancer tissue microarray by in situ hybridization and found that it was significantly downregulated in pancreatic cancer tissues compared to matched benign tissues .…”

Section: Discussionmentioning

confidence: 99%

“…The latest studies showed that microRNAs have interaction with the tumour microenvironment via a variety of molecular pathways. [31][32][33] Shi et al investigated the expression profile of miR-1247-5p in pancreatic cancer tissue microarray by in situ hybridization and found that it was significantly downregulated in pancreatic cancer tissues compared to matched benign tissues. 14 The different expression pattern in pancreatic cancer tissues and in pancreatic juice from pancreatic cancer patients may be explained by above tumour microenvironment influence.…”

Section: Discussionmentioning

confidence: 99%

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Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

Zhang

Fan

et al. 2018

Int J Experimental Path

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SummaryOur study aimed to clarify the correlation between miR‐1247‐5p expression and clinicopathological parameters and survival of patients with breast cancer (BC). We evaluated the expression level of miR‐1247‐5p in 224 formalin‐fixed, paraffin‐embedded specimens (112 BC and matched cancer free tissues) by quantitative real‐time reverse transcriptase polymerase chain reaction (qRT‐PCR). miR‐1247‐5p expression in BC tissues was found to be decreased compared with matched normal tissues (P < 0.01). Additionally, low miR‐1247‐5p expression in BC tissues was significantly associated with the advanced TNM stage (P = 0.007), lymph node metastasis (P = 0.015), poorer pathological differentiation (P = 0.005) and molecular subtype (P = 0.027). The patients in the low miR‐1247‐5p group had a shorter disease‐free survival and overall survival than those in the high miR‐1247‐5p group (P < 0.01). Furthermore, the univariate and the multivariate analyses showed that miR‐1247‐5p expression was an independent predictor of overall survival (P < 0.01). Our study showed that miR‐1247‐5p was related to the biological behaviour of breast tumour and prognosis of patients with BC. miR‐1247‐5p could be a novel tumour suppressor and act as a potential biomarker and therapeutic agent for breast carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

Zhang

Fan

et al. 2018

Int J Experimental Path

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“…Exosomes shed by pancreatic cancer cells can be internalized by CD14 + monocytes and impart a monocytic MDSC phenotype by downregulating HLA-DR expression and activating signal transducer and activator of transcription 3 (STAT3) signaling, with increased arginase I and ROS production as a result [ 153 ]. Another study reported that exosomes secreted by pancreatic cancer cells could expand both granulocytic and monocytic populations of MDSCs while lowering the number of dendritic cells, and proposed altered intracellular calcium fluxes as a potential mechanistic explanation [ 177 ]. The specific contents of pancreatic cancer cell-derived exosomes that govern the observed reprogramming of monocytes is presently unclear.…”

Section: Introductionmentioning

confidence: 99%

The hepatic pre-metastatic niche in pancreatic ductal adenocarcinoma

Houg

Bijlsma

2018

Mol Cancer

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies to date, largely because it is associated with high metastatic risk. Pancreatic tumors have a characteristic tendency to metastasize preferentially to the liver. Over the past two decades, it has become evident that the otherwise hostile milieu of the liver is selectively preconditioned at an early stage to render it more conducive to the engraftment and growth of disseminated cancer cells, a concept defined as pre-metastatic niche (PMN) formation. Pancreatic cancer cells exploit components of the tumor microenvironment to facilitate their migration out of the primary tumor, which often involves conversion of pancreatic cancer cells from an epithelial to a mesenchymal phenotype via the epithelial-to-mesenchymal transition. Pancreatic stellate cells and matrix stiffness have been put forward as major drivers of invasiveness in PDAC. Even before the onset of pancreatic cancer cell dissemination, soluble factors and extracellular vesicles secreted by the primary tumor, and possibly even premalignant lesions, help shape a supportive niche in the liver by providing vascular docking sites for circulating tumor cells, enhancing vascular permeability, remodeling the extracellular matrix and recruiting immunosuppressive inflammatory cells. Emerging evidence suggests that some of these tumor-derived factors may represent powerful diagnostic or prognostic biomarkers. Though our understanding of the mechanisms driving PMN formation in PDAC has expanded considerably, many outstanding questions and challenges remain. Further studies dissecting the molecular and cellular events involved in hepatic PMN formation in PDAC will likely improve diagnosis and open new avenues from a therapeutic standpoint.

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“…Moreover, miR-494-3p might suppress prostate cancer progression and metastasis by post-transcriptional regulation to CXCR4 mRNA 18 . However, function and characterization of miR-494-3p in patients with HCC has not been investigated and remains unclear 19 – 21 .…”

Section: Introductionmentioning

confidence: 99%

MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN

Lin

Huang

Liu

et al. 2018

Sci Rep

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Recent studies have shown that miR-494-3p is oncogene and has a central role in many solid tumors; however, the role of miR-494-3p in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, it was found that miR-494-3p was up-regulated in HCC tissues. The high level of miR-494-3p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. Functional study demonstrated that miR-494-3p significantly promoted HCC cell metastasis in vitro and vivo. Since phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) signaling is a basic oncogenic driver in HCC, a potential role of miR-494-3p was explored as well as its target genes in PI3K/AKT activation. Of all the predicted target genes of miR-494-3p, the tumor-suppressor phosphatase and tensin homolog (PTEN) were identified. In conclusion, the data we collected could define an original mechanism of PI3K/AKT hyperactivation and sketch the regulatory role of miR-494-3p in suppressing the expression of PTEN. Therefore, targeting miR-494-3p could provide an effective therapeutic method for the treatment of the disease.

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PDAC-derived exosomes enrich the microenvironment in MDSCs in a SMAD4-dependent manner through a new calcium related axis

Cited by 56 publications

References 50 publications

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

The hepatic pre-metastatic niche in pancreatic ductal adenocarcinoma

MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN

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