Growth inhibition of murine melanoma and human colon carcinoma by recombinant human platelet factor 4.
Although it is well established that angiogenesis is essential to tumor development, no human protein with high specificity and efficacy for prevention of angiogenesis has been characterized. In a previous study, we demonstrated that recombinant platelet factor 4 (rPF 4) inhibited angiogenesis in the chicken chorioallantoic membrane. In the present study, we have extended that finding to the use of recombinant human platelet factor 4 (rHuPF 4) to inhibit solid tumor growth in the mouse. rHuPF 4 effectively suppressed the growth of the B16-F10 murine melanoma in syngeneic C57BL/6J hosts and prevented the growth of primary tumors of both B16-F10 murine melanoma and HCT 116 human colon carcinoma in semisyngeneic CByB6F1/J female athymic nude mice. These two transformed cell lines were completely insensitive to rHuPF 4 in vitro at levels (50 micrograms/mL) that extensively inhibit normal endothelial cell proliferation. The migration of human endothelial cells was also inhibited at these concentrations of rHuPF 4, suggesting a second mechanism by which rHuPF 4 may modulate capillary development. The observed antitumor effects of rHuPF 4 might be due to the inhibition of angiogenesis. This finding could have implications for the development of novel therapeutic approaches to angiogenic diseases. Alternative, and possibly concurrent, mechanisms of the rHuPF 4 antitumor effect include lymphokine-activated killer cell activation and the induction of other cytokines.
Sharpe
R J
RJ
Repligen Corporation, Cambridge, MA 02139.
Byers
H R
HR
Scott
C F
CF
Bauer
S I
SI
Maione
T E
TE
D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010978:Platelet Factor 4 / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D010978:Platelet Factor 4