Augmentation of antimetastatic activity of interferon and tumor necrosis factor by heparin.
Interferon (IFN) and tumor necrosis factor (TNF) suppress the development of experimental metastasis and when used together, TNF and IFN show synergistic activity. However, the use of TNF is limited by its ability to initiate inappropriate hemostasis. Hemostatic effects are exaggerated by the procoagulant activity of certain tumor cell lines. Therapy with anticoagulants are indicated to block the effects of tumor cell products as well as chemotherapeutic side effects. Heparin is a glycosaminoglycan with diverse biological activity, including the ability to rapidly accelerate the inactivation of active clotting factors. The present studies have explored the therapeutic effects of combining heparin with TNF or interferon on experimental metastasis in mice using a melanoma cell line (B16BL6). Our data indicate that continued heparinization augments the antitumor activity of both interferon and TNF. Alterations of the hemostatic and immune systems play a role in the producing the observed effect.
Sylvester
D M
DM
Graduate Program in Pharmacology/Toxicology, College of Pharmacy, Washington State University, Pullman 99164.
Liu
S Y
SY
Meadows
G G
GG
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001777:Blood Coagulation / Q000187:drug effects; D004341:Drug Evaluation; D004357:Drug Synergism; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000503:physiopathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006493:Heparin