Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer. (10th September 2019)

• Record Type: Journal Article
• Authors: Zhang, Bin; Ye, Huilin; Ren, Xiaofan; Zheng, Shangyou; Zhou, Quanbo; Chen, Changhao; Lin, Qing; Li, Guolin; Wei, Lusheng; Fu, Zhiqiang; Zhang, Yuting; Hu, Chonghui; Li, Zhihua; Chen, Rufu
• Is Part Of: Cancer letters. Volume 459(2019)
• Page Start: 204
• Page End: 215
• Publication Date: 2019-09-10
• Subjects: Pancreatic ductal adenocarcinoma -- Cancer stem cell -- Tumor-associated macrophage -- Integrin -- Biomarker; PDAC Pancreatic ductal adenocarcinoma -- CSCs Cancer stem cells -- MDSCs Myeloid-derived suppressor cells -- TAMs Tumor-associated macrophages -- IHC Immunohistochemistry -- TCGA The Cancer Genome Atlas -- PSCs Pancreatic stellate cells -- KIRC Kidney renal clear cell carcinoma -- GBM Glioblastoma multiforme -- LGG Brain lower grade glioma -- ESCA Esophageal carcinoma -- THCA Thyroid carcinoma -- PAAD Pancreatic adenocarcinoma -- HNSC Head and neck squamous cell carcinoma -- LUSC Lung squamous cell carcinoma -- CHOL Cholangiocarcinoma -- KICH Kidney chromophobe -- BRCA Breast invasive carcinoma -- SARC Sarcoma -- LUAD Lung adenocarcinoma -- STAD Stomach adenocarcinoma -- CESC Cervical squamous cell carcinoma and endocervical adenocarcinoma -- SKCM Skin cutaneous melanoma -- KIRP Kidney renal papillary cell carcinoma -- PRAD Prostate adenocarcinoma -- READ Rectal adenocarcinoma -- BLCA Bladder urothelial carcinoma -- COAD Colon adenocarcinoma -- OV Ovarian serous cystadenocarcinoma -- PCPG Pheochromocytoma and paraganglioma -- UCEC Uterine corpus endometrial carcinoma -- UCS Uterine carcinosarcoma -- ACC Adrenocortical carcinoma -- THYM Thymoma -- LAML Acute myeloid leukemia -- TGCT Testicular germ cell tumors -- LIHC Liver hepatocellular carcinoma -- DLBC Lymphoid neoplasm diffuse large B cell lymphoma; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.06.005
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Graphical abstract: Image 1 Highlights: CD51 is overexpressed in macrophages rather than cancer cells. CD51 promotes M2 type polarization of macrophages. CD51 increases the secretion of TGF-β1 in Macrophages. CD51/TGF-β1/smad2/3 axis promotes the stemness of pancreatic cancer cells.