Abstract
We established five clones (ML‐01, ML‐02, MH‐01, MH‐02, MH‐03) from murine 3‐methylcholan‐threne‐induced fibrosarcoma A (Meth A), and investigated their experimental metastatic potentials in relation to their platelet‐aggregating activities. A clone with a high metastatic potential (MH‐02) showed a characteristic biphasic pattern of platelet aggregation, of which the first peak was not present in the aggregation patterns of the clone with low metastatic potential (ML‐01). The first peak was eliminated by treatment of the cells with apyrase, indicating that adenosine diphosphate (ADD was the causative substance of this particular peak. The metastatic potential of clones correlated well with the ADP concentration of the culture media. These results suggest that the increased ADP production and consequential enhancement of platelet‐aggregating activity are closely related to the increment of pulmonary metastatic potential of MH‐02 clone.
Keywords: Platelet aggregation, ADP, Highly metastatic clone
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REFERENCES
- 1. ) Gasic , G. J. and Gasic , T. B.Removal of sialic acid from the cell coat in tumor cells and vascular emdothelium, and its effects on metastasis . Pmc. Natl. Acad. Sci. USA , 48 , 1172 – 1177 ( 1962. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. ) Gasic , G. J. , Gasic , T. B. and Stewart , C. C.Anti‐metastatic effects associated with platelet reduction . Proc. Natl. Acad. Sci. USA , 61 , 46 – 52 ( 1968. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. ) Hilgard , P.The role of blood platelets in experimental metastasis . Br. J. Cancer , 28 , 429 – 435 ( 1973. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. ) Gastpar , H.Platelet‐cancer cell interaction in metastasis formation: a possible therapeutic approach to metastasis prophylaxis . J. Med. , 8 , 103 – 113 ( 1977. ). [PubMed] [Google Scholar]
- 5. ) Pearlstein , E. , Salk , P. L. , Yogeeswaran , G. and Karpatkin , S.Correlation between spontaneous metastatic potential, platelet‐aggregating activity of cell surface extracts, and cell surface sialylation in 10 metastatic variant derivatives of rat renal sarcoma cell line . Proc. Nat. Acad. Sci. USA , 77 , 4336 – 4339 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. ) Hara , Y. , Steiner , M. and Baldini , M. D.Characterization of the platelet‐aggregating activity of tumor cells . Cancer Res. , 40 , 1217 – 1222 ( 1980. ). [PubMed] [Google Scholar]
- 7. ) Mohanty , D. and Hilgard , P.A new platelet aggregation material (PAM) in an experimentally induced rat fibro‐sarcoma . Thromb. Haemostasis , 51 , 192 – 195 ( 1984. ). [PubMed] [Google Scholar]
- 8. ) Pearlstein , E. , Ambrogio , C. , Gasic , G. and Karpatkin , S.Inhibition of platelet‐aggregating activity of two human adenocarcinomas of the colon and an anaplastic murine tumor with a specific thrombin inhibitor, dansylarginine N‐(3‐ethyl‐l,5‐pentanediyl) amide . Cancer Res. , 41 , 4535 – 4539 ( 1981. ). [PubMed] [Google Scholar]
- 9. ) Kitagawa , H. , Yamamoto , N. , Yamamoto , K. , Tanoue , K. , Kosaki , G. and Yamazaki , H.Involvement of platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa complex in thrombin‐dependentand‐independent platelet aggregations induced by tumor cells . Cancer Res. , 49 , 537 – 541 ( 1989. ). [PubMed] [Google Scholar]
- 10. ) Holme , R. , Oftelro , R. and Hovig , T.In vitro interaction between cultured cells and human blood platelets , Thromb. Haetnostasis , 40 , 89 – 102 ( 1978. ). [PubMed] [Google Scholar]
- 11. ) Bastida , E. , Ordinas , A. , Giardina , S. L. and Jamieson , G. A.Differentiation of platelet‐aggregating effects of human tumor cell lines based on inhibition studies with apyrase, hirudin, and phospholipase . Cancer Res. , 42 , 4348 – 4352 ( 1982. ). [PubMed] [Google Scholar]
- 12. ) Honn , K. F. , Cavanaugh , P. , Evens , C. , Taylor , J. D. and Sloane , B. F.Tumor cell‐platelet aggregation: induced by cathepsin B‐like proteinase and inhibited by prostacyclin . Science , 217 , 540 – 542 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Esumi , N. , Todo , S. and Imashuku , S.Platelet aggregating activity mediated by thrombin generation in the NCG human neuroblastoma cell line . Cancer Res. , 47 , 2129 – 2135 ( 1987. ). [PubMed] [Google Scholar]
- 14. ) Watanabe , M. , Okochi , E. , Sugimoto , Y. and Tsuruo , T.Identification of a platelet‐aggregating factor of murine colon adenocarcinoma 26: Mr 44,000 membrane protein as determined by monoclonal antibodies . Cancer Res. , 48 , 6411 – 6416 ( 1988. ). [PubMed] [Google Scholar]
- 15. ) Niitsu , Y. , Ishigaki , S. , Kogawa , K. , Mogi , Y. , Watanabe , N. , Kongo , Y. and Urushizaki , I.Effect of combined administration of a prostacyclin analogue and adriamycin against the artificial metastasis of Meth A cell . Invasion Metastasis , 8 , 57 – 72 ( 1988. ). [PubMed] [Google Scholar]
- 16. ) Grignani , G. and Jamieson , G. A.Platelet in tumor metastasis: generation of adenosine diphosphate by tumor cells is specific but unrelated to metastatic potential . Blood , 71 , 844 – 849 ( 1988. ). [PubMed] [Google Scholar]
- 17. ) Mahalingam , M. , Ugen , K. E. , Kao , K‐J. and Klein , P. A.Functional role of platelets in experimental metastasis studied with cloned murine fibrosarcoma cell variants . Cancer Res. , 88 , 1460 – 1464 ( 1988. ). [PubMed] [Google Scholar]
- 18. ) Yasuda , A. , Ashi , T. , Kato , M. and Uchida , K.A stereoselective synthesis of (R)‐fluoro‐PGI2 . In “ Challenging Frontiers for Prostaglandin Research ”, p. 44 ( 1984. ). Gendai Iryosha; , Tokyo . [Google Scholar]
- 19. ) Niitsu , Y. , Watanabe , N. , Umeno , H. , Sone , H. , Neda , H. , Yamauchi , N. , Maeda , M. and Urushizaki , I.Synergistic effects of recombinant human tumor necrosis factor and hyperthermia on in vitro cytotoxicity and artificial metastasis . Cancer Res. , 48 , 654 – 657 ( 1988. ). [PubMed] [Google Scholar]
- 20. ) Niitsu , Y. , Watanabe , N. , Yamauchi , N. , Maeda , M. , Kogawa , K. , Kuriyama , H. , Neda , H. and Sone , H.The antimetastatic effect of tumor necrosis factor on the artificial metastasis of high‐ and low‐metastatic clones derived from methylcholanthrene induced A fibrosarcoma cells . Cancer J. , 2 , 91 – 94 ( 1988. ). [Google Scholar]
- 21. ) Pearlstein , E. , Cooper , L. B. and Karpatkin , S.Extraction and characterization of a platelet aggregating material from SV40 transformed mouse 3T3 fibroblasts . J. Lab. Clin. Med. , 93 , 332 – 344 ( 1979. ). [PubMed] [Google Scholar]
- 22. ) Nunn , B.Some characteristics of mouse platelet aggregation and a comparison of the activity of a range of compounds in mouse and human platelet‐rich plasma in vitro . Thromb. Haemostasis , 45 , 1 – 5 ( 1981. ). [PubMed] [Google Scholar]
- 23. ) Watanabe , N. , Niitsu , Y. , Umeno , H. , Sone , H. , Neda , H. , Yamauchi , N. , Maeda , M. and Urushizaki , I.Synergistic cytotoxic and antitumor effects of recombinant human tumor necrosis factor and hyperthermia . Cancer Res. , 48 , 650 – 653 ( 1988. ). [PubMed] [Google Scholar]
- 24. ) Holmsen , H. , Storm , E , and Day , H. J.Determination of ATP and ADP in blood platelets: a modification of the firefly luciferase assay for plasma . Anal. Biochem. , 46 , 489 – 501 ( 1972. ). [DOI] [PubMed] [Google Scholar]
- 25. ) Niitsu , Y. , Mogi , Y. , Bannai , K. , Ishii , T. , Ishigaki , S. , Kumai , R. , Koshida , Y. , Kogawa , K. , Kongo , Y. and Urushizaki , I.Studies on platelet aggregation induced by humanculturedcarcinoma celllines . Jpn. J. Cancer Chemother. , 11 , 480 – 486 ( 1984. ) ( in Japanese ). [PubMed] [Google Scholar]