Biomaterial Database

Tumor cytotoxic activity of HGF-SF. 1993

K Higashio, and N Shima

Life Science Research Institute, Snow Brand Milk Products, Co., Ltd., Tochigi, Japan.

IMR-90 human embryonic lung fibroblasts secrete a tumor cytotoxic factor. This factor, termed F-TCF, is moderately cytotoxic in human tumor cell lines (KB, MCF-7, BG-1) and is very cytotoxic in mouse tumor cell lines (Sarcoma 180, Meth A sarcoma, P388). The cytotoxicity depends on the initial target cell number and is due to cytostasis rather than cytolysis. F-TCF was purified from conditioned medium by a combination of UF-concentration, CM sephadex C-50, Con A sepharose, Mono S cation-exchange and heparin sepharose chromatography and exhibited a molecular mass (M(r)) of 76 to 80 kD on SDS-PAGE under non-reducing conditions. F-TCF is a heterodimer composed of a large alpha-subunit with M(r) 52 to 56 kD and a small beta-subunit with M(r) 30 to 34 kD. F-TCF is a heparin-binding, heat-labile, basic glycoprotein (pI 7.4-8.6). Its activity is stable over the pH range of 6.0 to 9.0, but is completely lost after reduction with 2-mercaptoethanol. Protein sequencing indicates that the alpha-subunit is blocked at the aminoterminus. The primary amino acid sequences deduced from hepatocyte growth factor (HGF) cDNAs cloned from human placenta and liver cDNA libraries indicate that F-TCF is identical to the placenta type HGF in the aminoterminal sequence of the beta-subunit, but differs at two sites from the liver type HGF. Two forms of F-TCF cDNA were found in an IMR-90 human fibroblast cDNA library. One form was identical to placenta type HGF cDNA and the other was a variant with a 15 base pair deletion in the coding region. In addition, mRNA corresponding to the deleted form of cDNA was present in total RNA prepared from IMR-90 cells. F-TCF was thus identified as placenta type HGFs including a variant. The deleted form of recombinant HGF (rHGF) expressed in CHO cells had slightly lower heparin-binding affinity than did the intact form. Both rHGFs had almost the same dose-response curves for cytotoxicity in Sarcoma 180 or Meth A sarcoma cells. Moreover, rHGF (the deleted form) was cytotoxic in hepatocellular carcinoma cells (HepG2, Hep3B, H35). Dose-response curves for the stimulation of DNA synthesis in rat hepatocytes by HGFs were very similar up to about 12.5 ng/ml, but differed significantly at higher concentrations. The deleted form gave maximal activity in a dose range of 12.5 to 100 ng/ml and had about 1.4- to 1.9-fold higher specific activity in that range than the intact form did.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008113	Liver Neoplasms	Tumors or cancer of the LIVER.	Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006528	Carcinoma, Hepatocellular	A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.	Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia