scholarly journals Extracellular vesicles in pancreatic cancer progression and therapies

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Chao-Hui Chang ◽  
Siim Pauklin
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Delayed Diagnosis ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma ◽  
Cancer Hallmarks ◽  
Pancreatic Cancers

AbstractPancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide due to delayed diagnosis and limited treatments. More than 90% of all pancreatic cancers are pancreatic ductal adenocarcinoma (PDAC). Extensive communication between tumour cells and other cell types in the tumour microenvironment have been identified which regulate cancer hallmarks during pancreatic tumorigenesis via secretory factors and extracellular vesicles (EVs). The EV-capsuled factors not only facilitate tumour growth locally, but also enter circulation and reach distant organs to construct a pre-metastatic niche. In this review, we delineate the key factors in pancreatic ductal adenocarcinoma derived EVs that mediate different tumour processes. Also, we highlight the factors that are related to the crosstalk with cancer stem cells/cancer-initiating cells (CSC/CIC), the subpopulation of cancer cells that can efficiently metastasize and resist currently used chemotherapies. Lastly, we discuss the potential of EV-capsuled factors in early diagnosis and antitumour therapeutic strategies.

scholarly journals Omics Approaches in Pancreatic Adenocarcinoma

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1052
Author(s):  
Iranzu González-Boja ◽  
Antonio Viúdez ◽  
Saioa Goñi ◽  
Enrique Santamaria ◽  
Estefania Carrasco-García ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Curative Intent ◽  
Pancreatic Cancers ◽  
Wide Range ◽  
Prevention And Treatment ◽  
Shed Light

Pancreatic ductal adenocarcinoma, which represents 80% of pancreatic cancers, is mainly diagnosed when treatment with curative intent is not possible. Consequently, the overall five-year survival rate is extremely dismal—around 5% to 7%. In addition, pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this area. Beyond the use of cytological or histological samples focusing in diagnosis, a plethora of new approaches are currently being used for a deeper characterization of pancreatic ductal adenocarcinoma, including genetic, epigenetic, and/or proteo-transcriptomic techniques. Accordingly, the development of new analytical technologies using body fluids (blood, bile, urine, etc.) to analyze tumor derived molecules has become a priority in pancreatic ductal adenocarcinoma due to the hard accessibility to tumor samples. These types of technologies will lead us to improve the outcome of pancreatic ductal adenocarcinoma patients.

scholarly journals An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

Cell Reports ◽  
2013 ◽  
Vol 3 (6) ◽  
pp. 2088-2099 ◽  
Author(s):  
Jungsun Kim ◽  
John P. Hoffman ◽  
R. Katherine Alpaugh ◽  
Andrew D. Rhim ◽  
Maximilian Reichert ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Progression ◽  
Ductal Adenocarcinoma ◽  
Ipsc Line

scholarly journals Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Biology ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 80 ◽  
Author(s):  
Etienne J. Slapak ◽  
JanWillem Duitman ◽  
Cansu Tekin ◽  
Maarten F. Bijlsma ◽  
C. Arnold Spek
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Treatment Response ◽  
Cancer Progression ◽  
Matrix Metalloproteases ◽  
Ductal Adenocarcinoma ◽  
Matrix Metalloprotease ◽  
Genetic Ablation ◽  
Key Drivers ◽  
Tumor Growth And Metastasis

Pancreatic cancer is a dismal disorder that is histologically characterized by a dense fibrotic stroma around the tumor cells. As the extracellular matrix comprises the bulk of the stroma, matrix degrading proteases may play an important role in pancreatic cancer. It has been suggested that matrix metalloproteases are key drivers of both tumor growth and metastasis during pancreatic cancer progression. Based upon this notion, changes in matrix metalloprotease expression levels are often considered surrogate markers for pancreatic cancer progression and/or treatment response. Indeed, reduced matrix metalloprotease levels upon treatment (either pharmacological or due to genetic ablation) are considered as proof of the anti-tumorigenic potential of the mediator under study. In the current review, we aim to establish whether matrix metalloproteases indeed drive pancreatic cancer progression and whether decreased matrix metalloprotease levels in experimental settings are therefore indicative of treatment response. After a systematic review of the studies focusing on matrix metalloproteases in pancreatic cancer, we conclude that the available literature is not as convincing as expected and that, although individual matrix metalloproteases may contribute to pancreatic cancer growth and metastasis, this does not support the generalized notion that matrix metalloproteases drive pancreatic ductal adenocarcinoma progression.

scholarly journals Immune responses in pancreatic cancer may be restricted by prevalence of activated regulatory T-cells, dysfunctional and senescent T-cells

2020 ◽  
Author(s):  
Shivan Sivakumar ◽  
Enas Abu-Shah ◽  
David J Ahern ◽  
Edward H Arbe-Barnes ◽  
Nagina Mangal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Regulatory T Cell ◽  
Rational Design ◽  
Tumour Microenvironment ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma

AbstractObjectivePancreatic cancer has the worst prognosis of any human malignancy and leukocyte infiltration is a major prognostic marker of the disease. As current immunotherapies confer negligible survival benefits, there is a need to better characterise leukocytes in pancreatic cancer to identify better therapeutic strategies.DesignIn this study, a multi-parameter mass-cytometry analysis was performed on 32,000 T-cells from eight human pancreatic cancer patients. Single-cell RNA sequencing dataset analysis was performed on a cohort of 24 patients. Multiplex immunohistochemistry imaging and spatial analysis were performed to map immune infiltration into the tumour microenvironment.ResultsRegulatory T-cell populations demonstrated highly immunosuppressive states with high TIGIT, ICOS and CD39 expression. CD8+ T-cells were found to be either in senescence or an exhausted state. The exhausted CD8 T-cells had low PD-1 expression but high TIGIT and CD39 expression. These findings were corroborated in an independent pancreatic cancer single-cell RNA dataset from 24 patients.ConclusionsThese data suggest that T-cells are major players in the suppressive microenvironment of pancreatic cancer. Our work identifies novel therapeutic targets that should form the basis for rational design of a new generation of clinical trials in pancreatic ductal adenocarcinoma.Statement of SignificanceThis study elucidates the T-cell phenotypes in pancreatic ductal adenocarcinoma (PDAC). T-cells potentiate immune-suppression through an activated regulatory T-cell population expressing high TIGIT, ICOS and CD39. CD8+ T-cells were primarily senescent or TIGIT+ exhausted, but with minimal PD-1 expression. These findings propose new immunotherapy targets for PDAC.

scholarly journals An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

Cell Reports ◽  
2013 ◽  
Vol 4 (2) ◽  
pp. 403 ◽  
Author(s):  
Jungsun Kim ◽  
John P. Hoffman ◽  
R. Katherine Alpaugh ◽  
Andrew D. Rhim ◽  
Maximilian Reichert ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Progression ◽  
Ductal Adenocarcinoma ◽  
Ipsc Line

scholarly journals Tumour–adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160485 ◽  
Author(s):  
Lucía Robado de Lope ◽  
Olwen Leaman Alcíbar ◽  
Ana Amor López ◽  
Marta Hergueta-Redondo ◽  
Héctor Peinado
Keyword(s):  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Breast And Ovarian Cancer ◽  
Tumour Metastasis ◽  
Bone Marrow Derived Cells

During metastasis, tumour cells must communicate with their microenvironment by secreted soluble factors and extracellular vesicles. Different stromal cell types (e.g. bone marrow–derived cells, endothelial cells and fibroblasts) influence the growth and progression of tumours. In recent years, interest has extended to other cell types in the tumour microenvironment such as adipocytes and adipose tissue–derived mesenchymal stem cells. Indeed, obesity is becoming pandemic in some developing countries and it is now considered to be a risk factor for cancer progression. However, the true impact of obesity on the metastatic behaviour of tumours is still not yet fully understood. In this ‘Perspective’ article, we will discuss the potential influence of obesity on tumour metastasis, mainly in melanoma, breast and ovarian cancer. We summarize the main mechanisms involved with special attention to the role of extracellular vesicles in this process. We envisage that besides having a direct impact on tumour cells, obesity systemically preconditions the tumour microenvironment for future metastasis by favouring the formation of pro-inflammatory niches. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

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