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Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer.
- Source :
-
Cancer letters [Cancer Lett] 2019 Sep 10; Vol. 459, pp. 204-215. Date of Electronic Publication: 2019 Jun 12. - Publication Year :
- 2019
-
Abstract
- Macrophage-targeted therapy offers new options for intractable pancreatic ductal adenocarcinoma (PDAC), which has a low 5-year survival rate. However, the factors regulating the biological function and phenotype of macrophages in PDAC are incompletely understood. Here, we found that CD51 was positively associated with the poor prognosis of PDAC patients and was highly expressed on macrophages but not on pancreatic cancer cells. Subsequently, we found that CD51 was a marker of macrophages, which promoted the stemness of pancreatic cancer cells. Furthermore, knockdown of CD51 in macrophages drove macrophages toward an M1-like phenotype. Mechanistically, macrophage-expressed CD51 contributed to the acquisition of stemness traits of pancreatic cancer cells by regulating the TGF-β1/smad2/3 pathway. Our data demonstrate the central role played by macrophage-expressed CD51 in the acquisition of stemness traits of pancreatic cancer cells through the paracrine induction of TGF-β1. We first show the connection between the CD51/TGF-β1/smad2/3 axis and PDAC cancer stem cell properties and then indicate that CD51-targeted therapy is a new therapeutic modality for PDAC.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Carcinoma, Pancreatic Ductal metabolism
Carcinoma, Pancreatic Ductal pathology
Cell Line, Tumor
Cell Polarity immunology
Female
Humans
Integrin alphaV immunology
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells pathology
Pancreatic Neoplasms metabolism
Pancreatic Neoplasms pathology
Prognosis
Signal Transduction
THP-1 Cells
Up-Regulation
Carcinoma, Pancreatic Ductal immunology
Integrin alphaV biosynthesis
Macrophages immunology
Neoplastic Stem Cells immunology
Pancreatic Neoplasms immunology
Smad2 Protein metabolism
Smad3 Protein metabolism
Transforming Growth Factor beta1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 459
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 31199988
- Full Text :
- https://doi.org/10.1016/j.canlet.2019.06.005