title: Parenchymal-stromal switching for extracellular matrix production on invasion of oral squamous cell carcinoma.
abstract: It is poorly understood which cell type, tumor cells, or stromal cells are responsible for the production of extracellular matrix molecules in the neoplastic stroma. We studied the expression of 4 extracellular matrix molecules at the protein and messenger RNA levels in monocellular and 2 kinds of coculture systems between human squamous cell carcinoma (ZK-1) and fibroblast (OF-1) cell lines, which may correspond to carcinoma in situ and squamous cell carcinoma, respectively. Squamous cell carcinoma and carcinoma in situ tissue sections were also investigated by immunohistochemistry and in situ hybridization for extracellular matrix. Immunohistochemically, perlecan and tenascin C were localized in carcinoma cells in carcinoma in situ, whereas they were in the stromal space in squamous cell carcinoma. In monocellular culture conditions, expression levels for perlecan, tenascin C, and laminin were more predominant in ZK-1 than in OF-1, although those for fibronectin were more enhanced in OF-1. However, these extracellular matrix expression levels of OF-1 were elevated, whereas those of ZK-1 dropped when they were in coculture conditions. The differences between ZK-1 and OF-1 were significantly more evident in direct contact (ZK-1/OF-1, 56%-22%) than in indirect contact (63%-39%). These results indicate that oral squamous cell carcinoma cells produce extracellular matrix in the absence of stromal fibroblasts (or in carcinoma in situ) and that they stop producing extracellular matrix in the presence of fibroblasts (or in squamous cell carcinoma). It is hence suggested that stromal fibroblasts after direct contact with invading squamous cell carcinoma cells are more responsible than squamous cell carcinoma cells for the formation of neoplastic stroma, whereas carcinoma in situ cells have to produce and deposit extracellular matrix by themselves to form intraepithelial microstromal spaces.
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
authors.forename: Hamdy
authors.initials: H
authors.lastname: Metwaly
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsuneki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abé
authors.forename: Kai Yu
authors.initials: KY
authors.lastname: Jen
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
mesh_terms: D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D061346:Laser Capture Microdissection; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D019063:Tenascin / Q000235:genetics / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D012333:RNA, Messenger; D019063:Tenascin; C071927:perlecan