Interleukin-1 beta and transforming growth factor-beta 3 cooperate to activate matrix metalloproteinase expression and invasiveness in A549 lung adenocarcinoma cells.
Cytokines present in the tumor microenvironment can promote the invasiveness and metastatic potential of cancer cells. We therefore investigated the effects of interleukin-1 beta (IL-1B) and transforming growth factor beta-3 (TGFB3) on the non-small cell lung carcinoma (NSCLC) cell line A549. We found that these cytokines synergistically activated matrix metalloproteinase (MMP)-1, MMP-3, and MMP-10 gene expression in these cells through mitogen-activated protein kinase (MAPK)-dependent pathways. Consistent with this, both cytokines stimulated epithelial to mesenchymal transition and MAPK-dependent invasion through Matrigel™. These studies identify IL-1B and TGFB3 as pro-invasive factors in NSCLC and potential therapeutic targets for tumor progression.
Research Service, Department of Veterans Affairs, White River Junction, VT 05009, United States.
Brenda L
BL
Petrella
David A
DA
Armstrong
Matthew P
MP
Vincenti
D000230:Adenocarcinoma / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002292:Carcinoma, Renal Cell / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003094:Collagen; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000473:pathology; D007797:Laminin; D008175:Lung Neoplasms / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D053506:Matrix Metalloproteinase 10 / Q000096:biosynthesis* / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011509:Proteoglycans; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*
D004338:Drug Combinations; D053583:Interleukin-1beta; D007797:Laminin; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011509:Proteoglycans; C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3; C059485:matrigel; D003094:Collagen; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10; D020781:Matrix Metalloproteinase 1