Influences of tumor stroma on the malignant phenotype.
BACKGROUND
The microenvironment makes a significant contribution to the progression of oral carcinomas. Many different stromal events, such as vascularization, fibroblast activation, myofibroblast differentiation, and the presence of specific stromal proteins, such as proteolytic enzymes, fibronectin and laminin 5 are all characteristics of the tumor stroma. Less is, however, known of the significance of the biophysical properties of the tumor stroma. The purpose of the present study was to investigate how cellular and mechanical properties of the three-dimensional collagen matrix may influence cell proliferation and invasion of oral carcinoma cell lines.


METHODS
Oral cancer cells were cultured in an organotypic culture system on different collagen concentrations, and invasion was measured. Furthermore, the presence of cancer associated proteins such as glycosylated oncofetal fibronectin and laminin 5 was investigated.


RESULTS
We found that expression of glycosylated oncofetal fibronectin was increased in the invasive phenotype of oral carcinoma cell lines. Furthermore we demonstrated that certain concentrations of collagen in the connective tissue equivalent, appears to stimulate invasiveness of oral carcinoma cells.
Nielsen
Jørgen Dau
JD
Department of Oral Diagnostics, Dental School, Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark.
Moeslund
Mette
M
Wandall
Hans H
HH
Dabelsteen
Sally
S
D000951:Antigens, Neoplasm / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D004777:Environment; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D000097794:Kalinin
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D003094:Collagen; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D000097794:Kalinin; C031192:oncofetal antigens