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Induction of invasion in an organotypic oral cancer model by CoCl 2 , a hypoxia mimetic
Author(s) -
Brusevold Ingvild J.,
Husvik Camilla,
Schreurs Olav,
Schenck Karl,
Bryne Magne,
Søland Tine M.
Publication year - 2010
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.2010.00720.x
Subject(s) - cancer cell , cancer , extracellular matrix , chemistry , kinase , malignancy , pathology , cell , cancer research , medicine , biochemistry
Brusevold IJ, Husvik C, Schreurs O, Schenck K, Bryne M, Søland TM. Induction of invasion in an organotypic oral cancer model by CoCl2, a hypoxia mimetic. Eur J Oral Sci 2010; 118: 168–176. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Invasion is a hallmark of malignancy. The aim of this study was to develop an in vitro model that can be used for experimental studies of cancer cell invasion. The organotypic oral cancer model was constructed by growing oral squamous cell carcinoma (OSCC) cells on a collagen matrix in which normal human fibroblasts were incorporated. Immunohistochemical staining of the model showed that the expression of invasion‐related molecules such as phosphorylated extracellular signal‐regulated kinases 1 and 2 (p‐ERK1/2), cyclooxygenase‐2 (COX‐2), p75 NTR , and hepatocyte growth factor receptor (Met) was similar to that seen in OSCC. Treatment of the model with cobalt chloride (CoCl 2 ) to mimic hypoxic conditions increased cancer cell invasion, defined as the appearance of cancer cell islands protruding into the matrix. Models treated with CoCl 2 showed increased expression of p75 NTR and laminin‐5 in the cancer cells, and a more pronounced fragmentation of collagen IV in the basal membrane area, in contrast to models that were left untreated. The results indicate that the present model is well suited for studies on cancer cell invasion in the matrix and that the addition of CoCl 2 on day 3 of the experiment is indicated because it markedly increases the invasion and improves the model.