title: Interleukin-32β stimulates migration of MDA-MB-231 and MCF-7cells via the VEGF-STAT3 signaling pathway.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Research Center for Women's Disease, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Park
authors.forename: Su Yun
authors.initials: SY
authors.lastname: Choi
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Maria
authors.initials: M
authors.lastname: Lee
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Nam
authors.forename: Ae Lee
authors.initials: AL
authors.lastname: Jeong
authors.forename: Sunyi
authors.initials: S
authors.lastname: Lee
authors.forename: Sora
authors.initials: S
authors.lastname: Han
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Yongil
authors.initials: Y
authors.lastname: Kwon
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D009367:Neoplasm Staging; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C496971:IL32 protein, human; D007378:Interleukins; D020033:Protein Isoforms; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042461:Vascular Endothelial Growth Factor A