title: Increased expression of the matrix metalloproteinase 2 in differentiating Tera 2 human embryonal carcinoma cells.
abstract: Secretion of proteolytic enzymes by cells has been implicated in tissue remodeling during embryonic development as well as in invasive neoplastic diseases. We studied the regulation of type-IV-collagenase activity in Tera 2 human embryonal carcinoma cells, which in the undifferentiated state proliferate rapidly and are tumorigenic. The undifferentiated cells produced relatively low levels of matrix-metalloproteinase-2 (MMP-2) activity. This activity was not markedly affected by exogenous basic fibroblast growth factor (bFGF) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA), even though the plasminogen activator activity of the cells was increased by these agents. Tera 2 cells can be induced by retinoic acid to differentiate into quiescent cells, of which many express neuronal characteristics. The type-IV-collagenase activity of the cells increased markedly during the differentiation. This increase was mainly due to increased expression of MMP-2. Expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was not markedly affected by the differentiation of Tera 2 cells. The results show that in the Tera 2 cell system, increased expression of MMP-2 is characteristic of the differentiated derivatives. This is in contrast with many other model systems, where increased type-IV-collagenase activity is associated with the malignant phenotype. This pattern of regulation may reflect the facts that Tera 2 cells resemble early embryonic cells and that their differentiation mimics related cell-differentiation processes in the developing embryo.
authors.affiliation: Department of Pathology, University of Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Tienari
authors.forename: L
authors.initials: L
authors.lastname: Pertovaara
authors.forename: O
authors.initials: O
authors.lastname: Saksela
authors.forename: E
authors.initials: E
authors.lastname: Lehtonen
authors.forename: T
authors.initials: T
authors.lastname: Vartio
mesh_terms: D018236:Carcinoma, Embryonal / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013268:Stimulation, Chemical; D018243:Teratocarcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D013736:Testicular Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D010960:Plasminogen Activators; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D013755:Tetradecanoylphorbol Acetate