title: Hypoxia enhances colon cancer migration and invasion through promotion of epithelial-mesenchymal transition.
abstract: BACKGROUND
  A hypoxic environment exists in most solid tumors because in rapidly growing tumors, the development of angiogenic vasculature is heterogenous, usually not enough to overcome the necessary oxygen supply. In an ischemic condition, cancer cells develop escape mechanisms to survive and leave the unfavorable environment. That result in the acquisition of increased potential for local invasion and evasion to distant organs. However, the escape mechanisms of cancer cells from hypoxic stress have not been fully characterized.
  
  
  METHODS
  The human colon cancer cell line LoVo was cultured in hypoxia, and the adhesive and migratory properties were analyzed. The expression of cell surface and cytoplasmic molecules was also investigated.
  
  
  RESULTS
  Under hypoxic conditions, cells developed epithelial-mesenchymal transition. The expression levels of α2, α5, and β1 integrins were significantly upregulated and, as a consequence, the ability to adhere to and migrate on collagen and fibronectin was increased. On the other hand, the expression of 67-kDa laminin receptor and the abilities to adhere to and migrate on laminin were decreased. Additionally, the expression of CXCR4 was significantly increased on cells cultured in hypoxia, and the chemotactic activity to stromal cell-derived factor 1α was remarkably increased.
  
  
  CONCLUSIONS
  Hypoxic stress induced active epithelial-mesenchymal transition in colon cancer cells, with the typical morphologic and functional changes. These morphologic and functional changes of β1 integrins, the 67-kDa laminin receptor, and CXCR4 may be essential for the acquisition of the invasive and metastatic features in colorectal cancer.
authors.affiliation: Department of Surgical Oncology, Faculty of Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. kimikh@attglobal.net
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hongo
authors.forename: Nelson H
authors.initials: NH
authors.lastname: Tsuno
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawai
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Sasaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Kaneko
authors.forename: Masaya
authors.initials: M
authors.lastname: Hiyoshi
authors.forename: Koji
authors.initials: K
authors.lastname: Murono
authors.forename: Noriko
authors.initials: N
authors.lastname: Tada
authors.forename: Takako
authors.initials: T
authors.lastname: Nirei
authors.forename: Eiji
authors.initials: E
authors.lastname: Sunami
authors.forename: Koki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D019718:Receptors, CXCR4 / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D005353:Fibronectins; D016023:Integrins; D019718:Receptors, CXCR4; D017474:Receptors, Laminin; D003094:Collagen