Galectin-1-driven upregulation of SDF-1 in pancreatic stellate cells promotes pancreatic cancer metastasis.
Galectin-1, mainly expressed in activated pancreatic stellate cells (PSCs), is involved in many important cancer-related processes. However, very little is known how Galectin-1 modulates PSCs and subsequently impacts pancreatic cancer cells (PCCs). Our chemokine antibody array and in vitro studies demonstrates that Galectin-1 induces secretion of stromal cell-derived factor-1(SDF-1) in PSCs by activating NF-κB signaling. The secreted SDF-1 increases migration and invasion of PCCs. Knockdown of Galectin-1 and inhibitor-mediated blockade of SDF-1 as well as its ligand CXCR4 and NF-κB verifies the findings. In vivo experiment by knockdown of Galectin-1 in PSCs further demonstrates the conclusion. Collectively, the present studies demonstrate that Galectin-1-driven production of SDF-1 in PSCs through activation of NF-κB promotes metastasis in PDAC, offering a potential target in the treatment of pancreatic cancer.
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China; Department of General Surgery, Affiliated Hospital of Nanjing University of TCM, Jiangsu Province Hospital of TCM, Nanjing 210029, China.
Dong
D
Qian
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.
Zipeng
Z
Lu
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China; Department of Gastroenterology, Subei People's Hospital, Clinical Medical School, Yangzhou University Affiliated Hospital, Yangzhou 225000, China.
Qingcheng
Q
Xu
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.
Pengfei
P
Wu
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.
Lei
L
Tian
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.
Liangtao
L
Zhao
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.
Baobao
B
Cai
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.
Jie
J
Yin
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.
Yang
Y
Wu
Department of Surgery, University of Missouri, Columbia, MO 65212, USA; Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, USA; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA.
Kevin F
KF
Staveley-O'Carroll
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China. Electronic address: jiangkuirong@njmu.edu.cn.
Kuirong
K
Jiang
Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China. Electronic address: miaoyi@njmu.edu.cn.
Yi
Y
Miao
Department of Surgery, University of Missouri, Columbia, MO 65212, USA; Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, USA. Electronic address: liguan@health.missouri.edu.
Guangfu
G
Li
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D034622:RNA Interference; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D037483:Galectin 1; C445499:LGALS1 protein, human; D016328:NF-kappa B; D019718:Receptors, CXCR4
Galectin-1; Metastasis; Pancreatic cancer; Pancreatic stellate cell; SDF-1