Significance of platelets in an antimetastatic activity of bacterial lipopolysaccharide.
Recently we reported an antimetastatic activity of bacterial lipopolysaccharide (LPS) on a NK-cell-resistant murine fibrosarcoma (NFSa). Here we investigate and report the mechanistic significance of platelets in this activity. The number of circulating platelets was reduced to 63% of the control 3 days after an i.v. injection of 1.0 micrograms LPS, and then recovered to the level of control at day 10. Aggregation efficiency of platelets was impaired by LPS. The number of metastatic lung colonies after an i.v. injection of tumor cells was maximally reduced to 2.2% of the control at day 3 and increased in proportion to the recovery of platelet number. Neuraminidase (Ndase), which caused a non-immunological thrombocytopenia, also inhibited lung metastasis when injected prior to an i.v. tumor cell challenge. LPS and Ndase showed an identical pattern against five other syngeneic tumors; these agents inhibited lung metastases of the FSa fibrosarcoma and the SCC VII squamous cell carcinoma but failed to inhibit those of the NR-S1 squamous cell carcinoma, the MMCa#4 mammary adenocarcinoma and the NR-PG parotid gland tumor. All the three cells which were not responsive to any agents possessed a high aggregating activity of platelets while the other three tumors responsive to both agents did not show a detectable level of this activity. Platelet transfusion failed to modify the antimetastatic activity of LPS. These results suggest that platelets play an important role in the antimetastatic activity of LPS, though whether the role is principal or assistant remains to be seen.
Kimoto
M
M
Division of Clinical Research, National Institute of Radiological Sciences, Chiba, Japan.
Ando
K
K
Koike
S
S
Matsumoto
T
T
Jibu
T
T
Moriya
H
H
Kanegasaki
S
S
D000818:Animals; D016913:Blood Component Transfusion; D008050:Lipid A / Q000494:pharmacology / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000097:blood / Q000503:physiopathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy; D009439:Neuraminidase / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
D008050:Lipid A; D008070:Lipopolysaccharides; D009439:Neuraminidase