title: SDF-1α upregulation of MMP-2 is mediated by p38 MAPK signaling in pancreatic cancer cell lines.
abstract: Pancreatic cancer is highly invasive and is currently the fourth leading cause of cancer death worldwide. CXC chemokine receptor-4 (CXCR4) is a G protein-coupled receptor for CXC chemokine ligand 12/stromal cell-derived factor-1α (SDF-1α), a member of a large family of small, structurally related, heparin-binding chemokine proteins. SDF-1α/CXCR4 plays an important role in tumor growth, invasion, metastasis, and angiogenesis. SDF-1α and CXCR4 are upregulated in many tumors, including pancreatic cancer tissues, and preliminary data indicate that the SDF-1/CXCR4 axis plays an important role in tumor invasion. However, their precise role and the mechanism through which they function remain largely unknown. In this study, analysis of SDF-1α, CXCR4 and MMP-2 expression in pancreatic cancer and adjacent tissue samples from ten patients revealed that all three proteins are overexpressed in human pancreatic cancer. SDF-1α induced MMP-2 and MMP-9 upregulation in PANC-1 and SW-1990 cells, which was associated with increased pancreatic cancer cell proliferation and invasion. Furthermore, SDF-1α induced p38 phosphorylation and p38 inhibition reduced both the level of SDF-1α-stimulated MMP-2 expression and PANC-1 cell invasion. Overall, our results demonstrate that SDF-1α/CXCR4 upregulates MMP-2 expression and induces pancreatic cancer cell invasion in PANC-1 and SW-1990 cell lines by activating p38 MAPK.
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Shijie
authors.initials: S
authors.lastname: Ma
authors.forename: Weike
authors.initials: W
authors.lastname: Cao
authors.forename: Haining
authors.initials: H
authors.lastname: Liu
authors.forename: Fengli
authors.initials: F
authors.lastname: Chen
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9