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British Journal of Cancer logoLink to British Journal of Cancer
. 1989 Apr;59(4):563–568. doi: 10.1038/bjc.1989.114

Growth-promoting effect of oestriol in a lymphoma lacking oestrogen receptors.

R Kawatsu 1, T Ezaki 1, M Kotani 1, M Akagi 1
PMCID: PMC2247142  PMID: 2713243

Abstract

Various doses (1 microgram to 10 mg) of oestriol (E3) were intraperitoneally injected into mice immediately after subcutaneous inoculation of an oestrogen receptor-negative lymphoma cell line (KE-5) established from a spontaneously developed AKR thymic lymphoma. The growth of KE-5 cells was markedly promoted by E3 at the early stage of tumour growth. At this stage, 1 microgram E3 enhanced tumour growth significantly and the maximum effect was obtained with 1 mg E3. Normal female mice showed a higher incidence and shorter latency than males. However, once tumours became palpable, the tumour growth rate appeared to be unaffected. Histological observations using Alcian blue and colloidal iron revealed a marked increase of hyaluronic acid in the subcutaneous connective tissue of the tumour-injection site within 3-5 days after intraperitoneal administration of 1 mg E3. Biochemical analyses showed a rapid and marked increase in skin hyaluronic acid content to over 3 times the control levels (0.25 +/- 0.10 mg g-1 skin) within 3 days of E3 administration. Subcutaneous inoculation of KE-5 cells together with hyaluronic acid (0.2 mg) resulted in markedly enhanced tumour growth, particularly at the early stage. These results suggest that an increase in stromal hyaluronic acid content is the most likely mechanism responsible for the promoting effect of E3 on KE-5 cells.

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Selected References

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  1. Bentley J. P., Brenner R. M., Linstedt A. D., West N. B., Carlisle K. S., Rokosova B. C., MacDonald N. Increased hyaluronate and collagen biosynthesis and fibroblast estrogen receptors in macaque sex skin. J Invest Dermatol. 1986 Nov;87(5):668–673. doi: 10.1111/1523-1747.ep12456427. [DOI] [PubMed] [Google Scholar]
  2. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clark J. H., Peck E. J., Jr Female sex steroids: receptors and function. Monogr Endocrinol. 1979;14:I-XII, 1-245. [PubMed] [Google Scholar]
  4. Farram E., Nelson D. S. Mouse mast cells as anti-tumor effector cells. Cell Immunol. 1980 Oct;55(2):294–301. doi: 10.1016/0008-8749(80)90162-8. [DOI] [PubMed] [Google Scholar]
  5. Fujii H., Hayama T., Kotani M. Stimulating effect of natural estrogens on proliferation of hepatocytes in adult mice. Acta Anat (Basel) 1985;121(3):174–178. doi: 10.1159/000145961. [DOI] [PubMed] [Google Scholar]
  6. Gorelik E., Wiltrout R. H., Brunda M. J., Holden H. T., Herberman R. B. Augmentation of metastasis formation by thioglycollate-elicited macrophages. Int J Cancer. 1982 May 15;29(5):575–581. doi: 10.1002/ijc.2910290514. [DOI] [PubMed] [Google Scholar]
  7. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  8. Gresser I., De Maeyer-Guignard J., Tovey M. G., De Maeyer E. Electrophoretically pure mouse interferon exerts multiple biologic effects. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5308–5312. doi: 10.1073/pnas.76.10.5308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Henderson W. R., Chi E. Y., Jong E. C., Klebanoff S. J. Mast cell-mediated tumor-cell cytotoxicity. Role of the peroxidase system. J Exp Med. 1981 Mar 1;153(3):520–533. doi: 10.1084/jem.153.3.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hosokawa M., Ishii M., Inoue K., Yao C. S., Takeda T. Estrogen induces different responses in dermal and lung fibroblasts: special reference to collagen. Connect Tissue Res. 1981;9(2):115–120. doi: 10.3109/03008208109160249. [DOI] [PubMed] [Google Scholar]
  11. Iwasaki K., Torisu M., Fujimura T. Malignant tumor and eosinophils. I. Prognostic significance in gastric cancer. Cancer. 1986 Sep 15;58(6):1321–1327. doi: 10.1002/1097-0142(19860915)58:6<1321::aid-cncr2820580623>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  12. Jong E. C., Klebanoff S. J. Eosinophil-mediated mammalian tumor cell cytotoxicity: role of the peroxidase system. J Immunol. 1980 Apr;124(4):1949–1953. [PubMed] [Google Scholar]
  13. Jung-Testas I., Bavard F., Baulieu E. E. Two sex steriod receptors in mouse fibroblasts in culture. Nature. 1976 Jan 15;259(5539):136–138. doi: 10.1038/259136a0. [DOI] [PubMed] [Google Scholar]
  14. Kotani M., Fujii H., Tsuchiya H., Matsuno K., Ekino S., Harada S. Effects of estrogen on the lymphoid regeneration and immune response in irradiated and marrow-reconstituted mice. Acta Anat (Basel) 1979;105(3):298–308. doi: 10.1159/000145134. [DOI] [PubMed] [Google Scholar]
  15. LEV R., SPICER S. S. SPECIFIC STAINING OF SULPHATE GROUPS WITH ALCIAN BLUE AT LOW PH. J Histochem Cytochem. 1964 Apr;12:309–309. doi: 10.1177/12.4.309. [DOI] [PubMed] [Google Scholar]
  16. Levy M. H., Wheelock E. F. The role of macrophages in defense against neoplastic disease. Adv Cancer Res. 1974;20:131–163. doi: 10.1016/s0065-230x(08)60110-4. [DOI] [PubMed] [Google Scholar]
  17. Luster M. I., Boorman G. A., Dean J. H., Luebke R. W., Lawson L. D. The effect of adult exposure to diethylstilbestrol in the mouse: alterations in immunological functions. J Reticuloendothel Soc. 1980 Dec;28(6):561–569. [PubMed] [Google Scholar]
  18. MOWRY R. W. Improved procedure for the staining of acidic polysaccharides by Müller's colloidal (hydrous) ferric oxide and its combination with the Feulgen and the periodic acid-Schiff reactions. Lab Invest. 1958 Nov-Dec;7(6):566–576. [PubMed] [Google Scholar]
  19. Martucci C., Fishman J. Uterine estrogen receptor binding of catecholestrogens and of estetrol (1,3,5(10)-estratriene-3,15alpha,16alpha,17beta-tetrol). Steroids. 1976 Mar;27(3):325–333. doi: 10.1016/0039-128x(76)90054-4. [DOI] [PubMed] [Google Scholar]
  20. Mukai M., Shinkai K., Tateishi R., Mori Y., Akedo H. Macrophage potentiation of invasive capacity of rat ascites hepatoma cells. Cancer Res. 1987 Apr 15;47(8):2167–2171. [PubMed] [Google Scholar]
  21. NICOL T., BILBEY D. L., CHARLES L. M., CORDINGLEY J. L., VERNON-ROBERTS B. OESTROGEN: THE NATURAL STIMULANT OF BODY DEFENCE. J Endocrinol. 1964 Oct;30:277–291. doi: 10.1677/joe.0.0300277. [DOI] [PubMed] [Google Scholar]
  22. Nishimura R., Kimura M., Tokunaga T., Akagi M. Measurement of nuclear estrogen receptors by charcoal adsorption: relationships of cytoplasmic and nuclear estrogen receptors and progesterone receptors in human breast cancer. Gan. 1982 Oct;73(5):713–720. [PubMed] [Google Scholar]
  23. Noble R. L., Beer C. T., Gout P. W. Evidence in vivo and in vitro of a role for the pituitary in the growth of malignant lymphomas in Nb rats. Cancer Res. 1980 Jul;40(7):2437–2440. [PubMed] [Google Scholar]
  24. REISSIG J. L., STORMINGER J. L., LELOIR L. F. A modified colorimetric method for the estimation of N-acetylamino sugars. J Biol Chem. 1955 Dec;217(2):959–966. [PubMed] [Google Scholar]
  25. Roche W. R. Mast cells and tumors. The specific enhancement of tumor proliferation in vitro. Am J Pathol. 1985 Apr;119(1):57–64. [PMC free article] [PubMed] [Google Scholar]
  26. Rochefort H., Capony F., Garcia M., Vignon F. The 52K estrogen-regulated protein secreted by breast cancer cells and its clinical potential. Ann N Y Acad Sci. 1986;464:190–201. doi: 10.1111/j.1749-6632.1986.tb16004.x. [DOI] [PubMed] [Google Scholar]
  27. Seaman W. E., Blackman M. A., Gindhart T. D., Roubinian J. R., Loeb J. M., Talal N. beta-Estradiol reduces natural killer cells in mice. J Immunol. 1978 Dec;121(6):2193–2198. [PubMed] [Google Scholar]
  28. Seaman W. E., Merigan T. C., Talal N. Natural killing in estrogen-treated mice responds poorly to poly I.C despite normal stimulation of circulating interferon. J Immunol. 1979 Dec;123(6):2903–2905. [PubMed] [Google Scholar]
  29. Sobel H., Lee K. D., Hewlett M. J. Effect of estrogen on acid glycosaminoglycans in skin of mice. Biochim Biophys Acta. 1965 Jul 1;101(2):225–229. doi: 10.1016/0926-6534(65)90056-4. [DOI] [PubMed] [Google Scholar]
  30. Takeuchi J. Growth-promoting effect of acid mucopolysaccharides on Ehrlich ascites tumor. Cancer Res. 1966 May;26(5):797–802. [PubMed] [Google Scholar]
  31. Tanaka A., Matsuoka H., Uemura H., Kakui Y., Imanishi T., Nishino H., Imanishi J. Production and characterization of tumor-degenerating factor. J Natl Cancer Inst. 1985 Mar;74(3):575–581. [PubMed] [Google Scholar]
  32. Tchernitchin A., Tchernitchin X. Characterization of the estrogen receptors in the uterine and blood eosinophil leukocytes. Experientia. 1976 Oct 15;32(10):1240–1242. doi: 10.1007/BF01953070. [DOI] [PubMed] [Google Scholar]
  33. Thompson J. S., Reilly R. W., Crawford M., Russe H. P. The effect of estradiol and estriol on the survival of sublethally and lethally irradiated mice. Radiat Res. 1965 Dec;26(4):567–583. [PubMed] [Google Scholar]
  34. Toole B. P., Biswas C., Gross J. Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6299–6303. doi: 10.1073/pnas.76.12.6299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Uno K., Shimizu S., Ido M., Naito K., Inaba K., Oku T., Kishida T., Muramatsu S. Direct and indirect effects of interferon on in vivo murine tumor cell growth. Cancer Res. 1985 Mar;45(3):1320–1327. [PubMed] [Google Scholar]
  36. Waltman S. R., Burde R. M., Berrios J. Prevention of corneal homograft rejection by estrogens. Transplantation. 1971 Feb;11(2):194–196. doi: 10.1097/00007890-197102000-00016. [DOI] [PubMed] [Google Scholar]
  37. Zava D. T., Goldhirsch A. Estrogen receptor in malignant melanoma: fact or artefact? Eur J Cancer Clin Oncol. 1983 Aug;19(8):1151–1159. doi: 10.1016/0277-5379(83)90041-x. [DOI] [PubMed] [Google Scholar]

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