Augmentation of tumor metastasis by platelet-activating factor.
The effect of platelet-activating factor (PAF) on experimental pulmonary metastasis by the B16F10 murine melanoma and the possible involvement of PAF in the activities of tumor necrosis factor alpha (TNF-alpha) and interleukin 1alpha (IL-1alpha) in tumor metastasis were investigated. i.p. injection of PAF enhanced the lung colonization in a dose- and time-dependent manner. PAF enhanced lung colonization when it was administered after, but not before, B16F10 inoculation. Multiple injections of PAF were more effective than a single injection. Neutralization of endogenous PAF with PAF antagonist BN50739 decreased lung colonization, suggesting that endogenous PAF plays an important role in pulmonary metastases. A single i.p. injection of TNF-alpha or IL-1alpha caused a marked enhancement in lung colonization. TNF-alpha- and IL-1alpha-mediated enhancement in lung colonies was significantly inhibited by BN50739. These results demonstrate that PAF has a metastasis-enhancing effect and is a mediator of the metastatic activities of TNF-alpha and IL-1alpha.
Im
S Y
SY
Department of Microbiology, Chunnam National University, Kwangju, Republic of Korea.
Ko
H M
HM
Kim
J W
JW
Lee
H K
HK
Ha
T Y
TY
Lee
H B
HB
Oh
S J
SJ
Bai
S
S
Chung
K C
KC
Lee
Y B
YB
Kang
H S
HS
Chun
S B
SB
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D001381:Azepines; D007375:Interleukin-1; D010972:Platelet Activating Factor; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C064509:BN 50739