title: Conditioned media of carcinoma cells cultured in hypoxic microenvironment stimulate angiogenesis in vitro; relationship to basic fibroblast growth factor.
abstract: Conditioned media (CM) harvested from human pulmonary squamous cell carcinoma (QG56), pulmonary small cell carcinoma (QG90) and gastric adenocarcinoma (MKN28) cultivated under hypoxic conditions (3% oxygen), enhanced the angiogenic activity in vitro more than those obtained under normoxic cultivation (20% oxygen). The total length of the tube structures formed by bovine capillary endothelial cells (BCEs) in the CM cultured at 3% oxygen was about 1.5 (QG56 and MKN28) or 1.9 (QG90) times longer than that at 20% oxygen. Tube formation was diminished by the preincubation of CM with anti-basic fibroblast growth factor (bFGF) IgG. After performing the fractionations of the CM and the crude extracts of cell lysates cultured using a heparin-Sepharose column, the mitogenic activity in the CM from all cancer cells at 3% oxygen was about twice that of CM at 20% oxygen, while it decreased in the cell lysates at 3% oxygen to about 40% of those at 20% oxygen. This mitogenic activity of BCEs in the CM from all cancer cells was almost totally suppressed by anti-bFGF IgG, but not with anti-vascular endothelial growth factor IgG. Hypoxia is an important factor in tumor angiogenesis by bFGF or bFGF-like molecule(s) derived from tumour cells.
authors.affiliation: First Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishibashi
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.forename: K
authors.initials: K
authors.lastname: Sueishi
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000503:physiopathology*; D002417:Cattle; D015687:Cell Hypoxia / Q000502:physiology*; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008222:Lymphokines / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D007074:Immunoglobulin G; D008222:Lymphokines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator