Metastatin: a hyaluronan-binding complex from cartilage that inhibits tumor growth.
In this study, a hyaluronan-binding complex, which we termed Metastatin, was isolated from bovine cartilage by affinity chromatography and found to have both antitumorigenic and antiangiogenic properties. Metastatin was able to block the formation of tumor nodules in the lungs of mice inoculated with B16BL6 melanoma or Lewis lung carcinoma cells. Single i.v. administration of Metastatin into chicken embryos inhibited the growth of both B16BL6 mouse melanoma and TSU human prostate cancer cells growing on the chorioallantoic membrane. The in vivo biological effect may be attributed to the antiangiogenic activity because Metastatin is able to inhibit the migration and proliferation of cultured endothelial cells as well as vascular endothelial growth factor-induced angiogenesis on the chorioallantoic membrane. In each case, the effect could be blocked by either heat denaturing the Metastatin or premixing it with hyaluronan, suggesting that its activity critically depends on its ability to bind hyaluronan on the target cells. Collectively, these results suggest that Metastatin is an effective antitumor agent that exhibits antiangiogenic activity.
Liu
N
N
Department of Oncology, Georgetown University Medical Center, Washington, DC 20007 USA.
Lapcevich
R K
RK
Underhill
C B
CB
Han
Z
Z
Gao
F
F
Swartz
G
G
Plum
S M
SM
Zhang
L
L
Green
S J
SJ
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002356:Cartilage / Q000737:chemistry; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006820:Hyaluronic Acid