1. Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer.
- Author
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Zhang B, Ye H, Ren X, Zheng S, Zhou Q, Chen C, Lin Q, Li G, Wei L, Fu Z, Zhang Y, Hu C, Li Z, and Chen R
- 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
- 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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