Abstract
We have found that two chemokines, recombinant gro-alpha and gro-beta, specifically inhibit growth factor-stimulated proliferation of capillary endothelial cells in a dose-dependent manner, whereas gro-gamma has no inhibitory effect. In vivo, gro-beta inhibits blood vessel formation in the chicken chorioallantoic membrane assay. It is sufficiently potent to effectively suppress basic fibroblast growth factor-induced corneal neovascularization after systemic administration in mice. Further, gro-beta significantly inhibits the growth of murine Lewis lung carcinoma in syngeneic C57B16/J and immunodeficient nude mice without toxicity. In vitro, Lewis lung carcinoma cells are completely insensitive to recombinant gro-beta at high concentrations that significantly inhibit endothelial cell proliferation. This finding supports the conclusion that gro-beta inhibits Lewis lung tumor growth by suppression of tumor-induced neovascularization.
MeSH Terms
Amino Acid Sequence
Animals
Carcinoma, Lewis Lung/drug therapy
Chemokine CXCL1
Chemokines/chemistry,pharmacology
Chemokines, CXC
Chemotactic Factors/pharmacology
Chick Embryo
Consensus Sequence
Growth Inhibitors/pharmacology
Growth Substances/pharmacology
Humans
Intercellular Signaling Peptides and Proteins
Mice
Mice, Inbred C57BL
Mice, Nude
Molecular Sequence Data
Neovascularization, Pathologic/prevention & control
Recombinant Proteins
Sequence Alignment
Sequence Homology, Amino Acid
Chemicals
CXCL1 protein, human
Chemokine CXCL1
Chemokines
Chemokines, CXC
Chemotactic Factors
Cxcl1 protein, mouse
Growth Inhibitors
Growth Substances
Intercellular Signaling Peptides and Proteins
Recombinant Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cao Y
Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA.
Chen C
Weatherbee J A
Tsang M
Folkman J
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