Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motility

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.

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Bcl-3 deficiency promotes cancer stem cell-ness and metastatic properties in pancreatic ductal adenocarcinoma

10.1055/s-0037-1604920 ◽

2017 ◽

Author(s):

SM Wörmann ◽

J Ai ◽

M Vallespinos ◽

KN Diakopoulos ◽

K Steiger ◽

...

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Pancreatic Ductal Adenocarcinoma ◽

Ductal Adenocarcinoma

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The extracellular matrix and focal adhesion kinase signaling regulate cancer stem cell function in pancreatic ductal adenocarcinoma

PLoS ONE ◽

10.1371/journal.pone.0180181 ◽

2017 ◽

Vol 12 (7) ◽

pp. e0180181 ◽

Cited By ~ 27

Author(s):

Asma Begum ◽

Theodore Ewachiw ◽

Clinton Jung ◽

Ally Huang ◽

K. Jessica Norberg ◽

...

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Cancer Stem Cell ◽

Pancreatic Ductal Adenocarcinoma ◽

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Cell Function ◽

Ductal Adenocarcinoma ◽

Kinase Signaling ◽

Focal Adhesion Kinase Signaling

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The IL-17A/IL-17RA Axis Is Not Related to Overall Survival and Cancer Stem Cell Modulation in Pancreatic Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21062215 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2215

Author(s):

Jiahui Li ◽

Christopher Betzler ◽

Philipp Lohneis ◽

Marie Christine Popp ◽

Jiwei Qin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Intraepithelial Neoplasia ◽

Ductal Adenocarcinoma ◽

Pancreatic Tumors ◽

Stem Cell Markers ◽

Sphere Formation

(1) Background: IL-17A accelerates pancreatic intraepithelial neoplasia (PanIN) progression. In this study, we examined whether IL-17A/IL-17RA promotes pancreatic ductal adenocarcinoma (PDAC) aggressiveness in terms of survival and cancer stem cell modulation. (2) Methods: In vitro, the wound-healing assay, the sphere formation assay, and flow cytometry were applied to assess cancer stem cell features. In vivo, pancreatic tumors were induced in C57BL/6 mice using electroporation with oncogenic plasmids (P53-/- R172H; KrasG12V). Anti-IL-17 antibodies were administered as immunotherapy. We analyzed IL-17A/IL-17RA related survival using publicly available transcriptomic data (n = 903). (3) Results: IL-17A/IL-17RA expression was not related to survival in PDAC patients. IL-17A neither induces stem cell markers nor increases sphere formation and cell motility in vitro. Blocking the IL-17A/IL-17RA axis in a murine pancreatic cancer model did not improve the survival of mice, but reduced the tumor burden slightly. (4) Conclusions: IL-17A does not promote stem cell expansion in PDAC cell lines. Blocking IL-17A/IL-17RA signaling does not interfere with pancreatic cancer development and progression and may not be considered as a promising monotherapy for PDAC.

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