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.

Credits:

Dong Quian^a,b,f, Zipeng Lu^a,b, Quingcheng Xu^a,b,g, Pengfei Wu^a,b, Lei Tian^a,b, Liangtao Zhao^a,b, Baobao Cai^a,b, Jie Yin^a,b, Yang Wu^a,b, Kevin F. Staveley-O’Carrol^c,d,e, Kuirong Jiang^a,b, Miao Yi^a,b, Guangfu Li^c,d

• a. Pancreas Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
• b. Pancreas Institute, Nanjing Medical University, Nanjing 210029, China
• c. Department of Surgery, University of Missouri, Columbia, MO 65212, USA
• d. Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, USA
• e. Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA
• f. Department of General surgery, Affiliated Hospital of Nanjing University of TCM, Jiangsu Province Hospital of TCM, Nanjing 210029, China
• g. Department of Gastroenterology, Subei Pople’s Hospital, Clinical Medical School, Yangzhou University Affiliated Hospital, Yangzhou 225000, China