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. 1994 Jun;69(6):1166–1170. doi: 10.1038/bjc.1994.229

Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency.

S Yamashita 1, J Yamashita 1, M Ogawa 1
PMCID: PMC1969450  PMID: 8198986

Abstract

Membrane-associated phospholipase A2 (M-PLA2) is an enzyme that hydrolyses the sn-2 fatty acyl ester bond of phosphoglycerides. We measured M-PLA2 concentration in tissue extracts from 325 human breast cancers using a specific radioimmunoassay recently developed. Correlation analyses between the tissue concentration of M-PLA2 and clinicopathological factors showed that the enzyme level was significantly higher in patients with distant metastasis than in those without. In addition, M-PLA2 concentration was significantly higher in scirrhous carcinoma than in other histological types. No significant association was found between M-PLA2 concentration and age, menstrual status, tumour size, histological grade, vessel involvement or oestrogen receptor (ER) and progesterone receptor (PR) status. The expression of M-PLA2 mRNA was examined in a fibroadenoma, a stage IV breast cancer and its metastatic site of skin. Northern blot analysis showed a clear hybridisation band corresponding to M-PLA2 mRNA in both primary breast cancer and its metastatic site, while the fibroadenoma expressed a faint band corresponding to M-PLA2 mRNA. Breast cancer patients with high M-PLA2 concentrations exhibited significantly shorter disease-free and overall survival than those with low M-PLA2 concentration at the cut-off point of 5 ng 100 mg-1 protein, which was determined in a separate study. In multivariate analysis, M-PLA2 was found to be an independent prognostic factor for disease recurrence and death in human breast cancer. The possible significance of M-PLA2 expression in human breast cancer tissue is discussed.

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Selected References

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  1. BLOOM H. J., RICHARDSON W. W. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957 Sep;11(3):359–377. doi: 10.1038/bjc.1957.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balch C. M., Dougherty P. A., Cloud G. A., Tilden A. B. Prostaglandin E2-mediated suppression of cellular immunity in colon cancer patients. Surgery. 1984 Jan;95(1):71–77. [PubMed] [Google Scholar]
  3. Clerc P., Bensaadi N., Pradel P., Estival A., Clemente F., Vaysse N. Lipid-dependent proliferation of pancreatic cancer cell lines. Cancer Res. 1991 Jul 15;51(14):3633–3638. [PubMed] [Google Scholar]
  4. Duffy M. J., Reilly D., O'Sullivan C., O'Higgins N., Fennelly J. J., Andreasen P. Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer. Cancer Res. 1990 Nov 1;50(21):6827–6829. [PubMed] [Google Scholar]
  5. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  6. Hara S., Kudo I., Inoue K. Augmentation of prostaglandin E2 production by mammalian phospholipase A2 added exogenously. J Biochem. 1991 Aug;110(2):163–165. doi: 10.1093/oxfordjournals.jbchem.a123550. [DOI] [PubMed] [Google Scholar]
  7. Heinrikson R. L., Krueger E. T., Keim P. S. Amino acid sequence of phospholipase A2-alpha from the venom of Crotalus adamanteus. A new classification of phospholipases A2 based upon structural determinants. J Biol Chem. 1977 Jul 25;252(14):4913–4921. [PubMed] [Google Scholar]
  8. Imagawa W., Bandyopadhyay G. K., Wallace D., Nandi S. Phospholipids containing polyunsaturated fatty acyl groups are mitogenic for normal mouse mammary epithelial cells in serum-free primary cell culture. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4122–4126. doi: 10.1073/pnas.86.11.4122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jänicke F., Schmitt M., Ulm K., Gössner W., Graeff H. Urokinase-type plasminogen activator antigen and early relapse in breast cancer. Lancet. 1989 Oct 28;2(8670):1049–1049. doi: 10.1016/s0140-6736(89)91070-2. [DOI] [PubMed] [Google Scholar]
  10. Kanda A., Ono T., Yoshida N., Tojo H., Okamoto M. The primary structure of a membrane-associated phospholipase A2 from human spleen. Biochem Biophys Res Commun. 1989 Aug 30;163(1):42–48. doi: 10.1016/0006-291x(89)92096-2. [DOI] [PubMed] [Google Scholar]
  11. Kurizaki T., Egami H., Murata K., Kiyohara H., Okazaki S., Yoshida N., Ogawa M. Membrane-associated phospholipase A2 stimulates DNA synthesis in two murine fibroblasts. Res Commun Chem Pathol Pharmacol. 1992 Oct;78(1):39–45. [PubMed] [Google Scholar]
  12. Matsuda Y., Ogawa M., Sakamoto K., Yamashita S., Kanda A., Kohno M., Yoshida N., Nishijima J., Murata A., Mori T. Development of a radioimmunoassay for human group-II phospholipase A2 and demonstration of postoperative elevation. Enzyme. 1991;45(4):200–208. doi: 10.1159/000468890. [DOI] [PubMed] [Google Scholar]
  13. McGuire W. L., De La Garza M., Chamness G. C. Evaluation of estrogen receptor assays in human breast cancer tissue. Cancer Res. 1977 Mar;37(3):637–639. [PubMed] [Google Scholar]
  14. Nolan R. D., Danilowicz R. M., Eling T. E. Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor. Mol Pharmacol. 1988 Jun;33(6):650–656. [PubMed] [Google Scholar]
  15. Okada F., Hosokawa M., Hasegawa J., Ishikawa M., Chiba I., Nakamura Y., Kobayashi H. Regression mechanisms of mouse fibrosarcoma cells after in vitro exposure to quercetin: diminution of tumorigenicity with a corresponding decrease in the production of prostaglandin E2. Cancer Immunol Immunother. 1990;31(6):358–364. doi: 10.1007/BF01741407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Seilhamer J. J., Pruzanski W., Vadas P., Plant S., Miller J. A., Kloss J., Johnson L. K. Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. J Biol Chem. 1989 Apr 5;264(10):5335–5338. [PubMed] [Google Scholar]
  17. Spyratos F., Maudelonde T., Brouillet J. P., Brunet M., Defrenne A., Andrieu C., Hacene K., Desplaces A., Rouëssé J., Rochefort H. Cathepsin D: an independent prognostic factor for metastasis of breast cancer. Lancet. 1989 Nov 11;2(8672):1115–1118. doi: 10.1016/s0140-6736(89)91487-6. [DOI] [PubMed] [Google Scholar]
  18. Tandon A. K., Clark G. M., Chamness G. C., Chirgwin J. M., McGuire W. L. Cathepsin D and prognosis in breast cancer. N Engl J Med. 1990 Feb 1;322(5):297–302. doi: 10.1056/NEJM199002013220504. [DOI] [PubMed] [Google Scholar]
  19. Uhl W., Büchler M., Nevalainen T. J., Deller A., Beger H. G. Serum phospholipase A2 in patients with multiple injuries. J Trauma. 1990 Oct;30(10):1285–1290. doi: 10.1097/00005373-199010000-00015. [DOI] [PubMed] [Google Scholar]
  20. Vadas P., Hay J. B. Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic changes in endotoxin shock. Can J Physiol Pharmacol. 1983 Jun;61(6):561–566. doi: 10.1139/y83-086. [DOI] [PubMed] [Google Scholar]
  21. Vadas P., Pruzanski W. Role of secretory phospholipases A2 in the pathobiology of disease. Lab Invest. 1986 Oct;55(4):391–404. [PubMed] [Google Scholar]
  22. Yamashita J., Horiuchi S., Kimura M., Nishimura R., Akagi M. Plasminogen activator as a functional marker for estrogen dependence in human breast cancer cells. Jpn J Cancer Res. 1986 Feb;77(2):177–181. [PubMed] [Google Scholar]
  23. Yamashita J., Ogawa M., Inada K., Yamashita S., Nakashima Y., Saishoji T., Nomura K. Breast cancer prognosis is poor when total plasminogen activator activity is low. Br J Cancer. 1993 Feb;67(2):374–378. doi: 10.1038/bjc.1993.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yamashita S., Yamashita J., Sakamoto K., Inada K., Nakashima Y., Murata K., Saishoji T., Nomura K., Ogawa M. Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells. Cancer. 1993 May 15;71(10):3058–3064. doi: 10.1002/1097-0142(19930515)71:10<3058::aid-cncr2820711028>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  25. van den Bosch H. Intracellular phospholipases A. Biochim Biophys Acta. 1980 Sep 30;604(2):191–246. doi: 10.1016/0005-2736(80)90574-x. [DOI] [PubMed] [Google Scholar]

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