Induction of invasion in an organotypic oral cancer model by CoCl2, a hypoxia mimetic.
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.
Brusevold
Ingvild J
IJ
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway. ingviljb@odont.uio.no
Husvik
Camilla
C
Schreurs
Olav
O
Schenck
Karl
K
Bryne
Magne
M
Søland
Tine M
TM
D015703:Antigens, CD / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D003094:Collagen; D024141:Collagen Type IV / Q000032:analysis; D003470:Culture Media; D051546:Cyclooxygenase 2 / Q000032:analysis; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D007633:Keratins / Q000032:analysis; D007797:Laminin / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D014062:Tongue Neoplasms / Q000473:pathology*; D055815:Young Adult
D015703:Antigens, CD; D024141:Collagen Type IV; D003470:Culture Media; C400567:LAMC2 protein, human; D007797:Laminin; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D003035:Cobalt; D007633:Keratins; D003094:Collagen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C018021:cobaltous chloride