BACKGROUND: IL-32 is known to play an important role in inflammatory and autoimmune disease responses. In addition to its role in these responses, IL-32 and its different isoforms have in recent years been implicated in the development of various cancers. As of yet, the role of IL-32 in breast cancer has remained largely unknown. RESULTS: By performing immunohistochemical assays on primary breast cancer samples, we found that the level of IL-32β expression was positively correlated with tumor size, number of lymph node metastases and tumor stage. In addition, we found that breast cancer-derived MDA-MB-231 cells exogenously expressing IL-32β exhibited increased migration and invasion capacities. These increased capacities were found to be associated with an increased expression of the epithelial mesenchymal transition (EMT) markers vimentin and Slug, the latter of which is responsible for the increase in vimentin transcription. To next investigate whether IL-32β enhances migration and invasion through a soluble factor, we determined the levels of several migration-stimulating ligands, and found that the production of VEGF was increased by IL-32β. In addition, we found that IL-32β-induced VEGF increased migration and invasion through STAT3 activation. CONCLUSION: The IL-32β-VEGF-STAT3 pathway represents an additional pathway that mediates the migration and invasion of breast cancer cells under the conditions of normoxia and hypoxia.
BACKGROUND:IL-32 is known to play an important role in inflammatory and autoimmune disease responses. In addition to its role in these responses, IL-32 and its different isoforms have in recent years been implicated in the development of various cancers. As of yet, the role of IL-32 in breast cancer has remained largely unknown. RESULTS: By performing immunohistochemical assays on primary breast cancer samples, we found that the level of IL-32β expression was positively correlated with tumor size, number of lymph node metastases and tumor stage. In addition, we found that breast cancer-derived MDA-MB-231 cells exogenously expressing IL-32β exhibited increased migration and invasion capacities. These increased capacities were found to be associated with an increased expression of the epithelial mesenchymal transition (EMT) markers vimentin and Slug, the latter of which is responsible for the increase in vimentin transcription. To next investigate whether IL-32β enhances migration and invasion through a soluble factor, we determined the levels of several migration-stimulating ligands, and found that the production of VEGF was increased by IL-32β. In addition, we found that IL-32β-induced VEGF increased migration and invasion through STAT3 activation. CONCLUSION: The IL-32β-VEGF-STAT3 pathway represents an additional pathway that mediates the migration and invasion of breast cancer cells under the conditions of normoxia and hypoxia.
Authors: K Vuoriluoto; H Haugen; S Kiviluoto; J-P Mpindi; J Nevo; C Gjerdrum; C Tiron; J B Lorens; J Ivaska Journal: Oncogene Date: 2010-11-08 Impact factor: 9.867
Authors: Guilian Niu; Kenneth L Wright; Mei Huang; Lanxi Song; Eric Haura; James Turkson; Shumin Zhang; Tianhong Wang; Dominic Sinibaldi; Domenico Coppola; Richard Heller; Lee M Ellis; James Karras; Jacqueline Bromberg; Drew Pardoll; Richard Jove; Hua Yu Journal: Oncogene Date: 2002-03-27 Impact factor: 9.867
Authors: P Felaco; M L Castellani; M A De Lutiis; M Felaco; F Pandolfi; V Salini; D De Amicis; J Vecchiet; S Tete; C Ciampoli; F Conti; G Cerulli; A Caraffa; P Antinolfi; C Cuccurullo; A Perrella; T C Theoharides; P Conti; E Toniato; D Kempuraj; Y B Shaik Journal: J Biol Regul Homeost Agents Date: 2009 Jul-Sep Impact factor: 1.711
Authors: J H Oh; M-C Cho; J-H Kim; S Y Lee; H J Kim; E S Park; J O Ban; J-W Kang; D-H Lee; J-H Shim; S B Han; D C Moon; Y H Park; D-Y Yu; J-M Kim; S H Kim; D-Y Yoon; J T Hong Journal: Oncogene Date: 2011-03-21 Impact factor: 9.867
Authors: Yvette J E Sloot; Katrin Rabold; Thomas Ulas; Dennis M De Graaf; Bas Heinhuis; Kristian Händler; Joachim L Schultze; Mihai G Netea; Johannes W A Smit; Leo A B Joosten; Romana T Netea-Maier Journal: Cell Oncol (Dordr) Date: 2019-06-14 Impact factor: 6.730
Authors: Audrey Player; Nissi Abraham; Kayla Burrell; Iria Ondo Bengone; Anthony Harris; Lisa Nunez; Telisa Willaims; Sharon Kwende; Wiley Walls Journal: Genes Cancer Date: 2017-07