A new in vitro model for analyzing the biological behavior of well-differentiated squamous cell carcinoma.
A suitable model analyzing the behavior of well-differentiated squamous cell carcinoma has not yet been established. We tried to establish such a system using a reconstructed oral mucosa, in which T3M-1 squamous cell carcinoma cells were cultured on 3T3 fibroblast-containing collagen gel. Fibroblasts promoted the stratification and keratinization of T3M-1 cells. During growth, the Ki-67 index of T3M-1 cells with fibroblasts was higher than that of T3M-1 cells alone. Fibroblasts increased the expression of involucrin, a differentiating marker of keratinocytes, in T3M-1 cells. They also promoted the invasion of T3M-1 cells into the gel. When T3M-1 cells alone were cultured in a fibroblast-conditioned (FC) medium, the fibroblast-induced phenomena mentioned above were almost replicated. In addition, epidermal growth factqr (EGF) promoted T3M-1 cells growth, but not the invasion. cDNA microarray analysis showed that FC medium increased the expression of EGF receptor and several other mRNAs of T3M-1 cells. The data suggest that T3M-1 cells, under cancer-stromal fibroblast interaction, undergo invasive growth with their well-differentiated squamous phenotype, and that this interaction may be mediated partly by soluble molecules (e.g., EGF) in an autocrine or paracrine pathway. Our system will probably provide a useful model for analyzing the biological behavior of well-differentiated squamous cell carcinoma.
Satoh
Shintaro
S
Department of Pathology and Biodefense, Division of Cellular and Molecular Pathology, Faculty of Medicine, Saga University, Saga 849-8501, Japan. satos3@med.saga-u.ac.jp
Toda
Shuji
S
Inokuchi
Akira
A
Sugihara
Hajime
H
D016475:3T3 Cells; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D003094:Collagen; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts; D005782:Gels; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011498:Protein Precursors / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D017154:Stromal Cells
D017077:Culture Media, Conditioned; D005782:Gels; D019394:Ki-67 Antigen; D011498:Protein Precursors; D017472:Receptors, Interleukin-1; C032253:involucrin; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D003094:Collagen