title: VCC-1, a novel chemokine, promotes tumor growth.
abstract: We have identified a novel human gene by transcriptional microarray analysis, which is co-regulated in tumors and angiogenesis model systems with VEGF expression. Isolation of cDNA clones containing the full-length VCC-1 transcript from both human and mouse shows a 119 amino acid protein with a 22 amino acid cleavable signal sequence in both species. Comparison of the protein product of this gene with hidden Markov models of all known proteins shows weak but significant homology with two known chemokines, SCYA17 and SCYA16. Northern analysis of human tissues detects a 1 kb band in lung and skeletal muscle. Murine VCC-1 expression can also be detected in lung as well as thyroid, submaxillary gland, epididymis, and uterus tissues by slot blot analysis. By quantitative real time RT-PCR 71% of breast tumors showed 3- to 24-fold up-regulation of VCC-1. In situ hybridization of breast carcinomas showed strong expression of the gene in both normal and transformed mammary gland ductal epithelial cells. In vitro, human microvascular endothelial cells grown on fibronectin increase VCC-1 expression by almost 100-fold. In addition, in the mouse angioma endothelial cell line PY4.1 the gene was over-expressed by 28-fold 6 h after induction of tube formation while quiescent and proliferating cells showed no change. VCC-1 expression is also increased by VEGF and FGF treatment, about 6- and 5-fold, respectively. Finally, 100% of mice injected with NIH3T3 cells over-expressing VCC-1 develop rapidly progressing tumors within 21 days while no growth is seen in any control mice injected with NIH3T3 cells containing the vector alone. These results strongly suggest that VCC-1 plays a role in angiogenesis and possibly in the development of tumors in some tissue types.
authors.affiliation: Department of Oncology Pharmacology, Pfizer Inc., 700 Chesterfield Parkway North, St. Louis, MO 63198, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinstein
authors.forename: Richard
authors.initials: R
authors.lastname: Head
authors.forename: David W
authors.initials: DW
authors.lastname: Griggs
authors.forename: Duo
authors.initials: D
authors.lastname: Sun
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Evans
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Swearingen
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Westlin
authors.forename: Richard
authors.initials: R
authors.lastname: Mazzarella
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019743:Chemokines, CXC; D017124:Conserved Sequence; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C508524:CXCL17 protein, human; D018925:Chemokines; D019743:Chemokines, CXC; C514992:VCC-1 protein, mouse