Summary
Primary diethylstilbestrol-induced kidney tumors from Syrian hamsters were grown in vitro and maintained in culture for 6 mo. Combined immunohistochemical studies using antibodies to intermediate filaments and ultrastructural studies of tumor cells in culture exhibited characteristics similar to tumor cells in vivo. Furthermore, the cells manifested transformed properties in culture; they grew both as multilayered colonies attached to the tissue culture substrate and as floating multicellular colonies (spheroids). When cultured cells were injected into diethylstilbestrol-treated recipient hamsters, tumors developed at the injection sites. In contrast, renal tubules or whole kidney cortex from control hamsters cultured in the same medium underwent only short-term growth, with senescence developing after approximately 1 mo. However, cell cultures of kidney cortex from animals treated in vivo for 5 mo. with diethylstilbestrol formed a cell line. This diethylstilbestrol-induced cell line has been maintained in culture for 1.5 yr and has the following characteristics: a) it is anchorage-dependent, b) it is negative in in vivo tumorigenicity tests, and c) cultured cells are histochemically and ultrastructurally similar to cultured tumor cells. This culture system should prove to be of use in studying hormonal carcinogenesis in vitro.
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Algard, F. T. Hormone-induced tumors. I. Hamster flank organ and kidney tumors in vitro. JNCI 25:557–571; 1960.
Barasch, J.; Koseki, C.; Al-Awquati, Q. Immortalization of renal stem cells. J. Am. Soc. Nephrol. 2:438; 1991.
Forsberg, J. G. Estrogen, vaginal cancer, and vaginal development. Am. J. Obstet. Gynecol. 113:83–87; 1977.
Forsberg, J. G. Neonatal estrogen treatment and epithelial abnormalities in the cervicovaginal epithelium of adult mice. Cancer Res. 41:721–734; 1981.
Freyer, J. P.; Schor, P. L. Regrowth kinetics of cells from different regions of multicellular spheroids of four cell lines. J. Cell Physiol. 138:384–392; 1989.
Gladek, A.; Liehr, J. G. Mechanism of genotoxicity of diethylstilbestrol in vivo. J. Biol. Chem. 264:16847–16852; 1989.
Gonzalez, A.; Oberley, T. D.; Li, J. J. Morphological and immunohistochemical studies of the estrogen-induced Syrian hamster renal tumor: probable cell of origin. Cancer Res. 49:1020–1028; 1989.
Gospodarowicz, D.; Lepine, J.; Massoglia, S., et al. Comparison of the ability of basement membranes produced by corneal endothelial and mouse-derived endodermal PF-HR-9 cells to support the proliferation and differentiation of bovine kidney tubule epithelial cells in vitro. J. Cell Biol. 99:947–961; 1984.
Haaf, H.; Li, J. J.; Li, S. A. Covalent binding of estrogen metabolites to hamster liver microsomal proteins: inhibition by ascorbic acid and catechol-O-methyl transferase. Carcinogenesis 8:209–215; 1987.
Haaf, H.; Metzler, M. Covalent binding of diethylstilbestrol to microsomal protein in vitro correlates with the organotropism of its carcinogenicity. Carcinogenesis 6:659–660; 1985.
Hacker, H. J.; Bannasch, P.; Liehr, J. G. Histochemical analysis of the estradiol-induced kidney tumors in male Syrian hamsters. Cancer Res. 48:971–976; 1988.
Herbst, A. L.; Aubhy, M. M.; Anderson, D. Neoplastic changes in the human female genital tract following intrauterine exposure to diethylstilbestrol. Prog. Cancer Res. Ther. 31:389–399; 1984.
Horning, E. S.; Whittick, J. W. The histogenesis of stilboestrol-induced renal tumors in the male golden hamster. Br. J. Cancer 8:451–457; 1954.
Kirkman, H. Autonomous derivatives of estrogen-induced renal carcinomas and spontaneous renal tumors in the Syrian hamster. Cancer Res. 34:2728–2740; 1974.
Kirkman, H.; Robbins, M. Estrogen-induced tumors of the kidney. V. Histology and histogenesis in the Syrian hamster. NCI Monogr. 1:93–139; 1959.
Koide, N.; Sakaguchi, K.; Koide, Y., et al. Formation of multicellular spheroids composed of adult rat hepatocytes in dishes with positively charged surfaces and under other non-adherent environments. Exp. Cell Res. 186:227–235; 1990.
Kwok, C. S.; Crivici, A.; MacGregor, W. D., et al. Optimization of radioimmunotherapy using human malignant melanoma multicell spheroids as a model. Cancer Res. 49:3276–3281; 1989.
Li, J. J.; Li, S. A. High yield of primary serially transplanted hamster renal carcinoma: steroid receptor and morphologic characteristics. Eur. J. Cancer 16:1119–1125; 1980.
Li, J. J.; Talley, D. J.; Li, S. A., et al. Receptor characteristics of specific estrogen binding in the renal adenocarcinoma of the golden hamster. Cancer Res. 36:1127–1132; 1976.
Li, J. J.; Li, S. A.; Cuthbertson, T. L. Nuclear retention of all steroid hormone receptor classes in the hamster renal carcinoma. Cancer Res. 39:2647–2651; 1979.
Li, S. A.; Klicka, J. K.; Li, J. J. Effect of androgen and estrogen treatment on hamster liver and kidney estrogen 2-/4-hydroxylase activity. Endocrinology 119:1810–1815; 1986.
Lin, Y. C.; Talley, D. J.; Villee, C. A. Dynamics of progesterone binding in nuclei and cytosol of estrogen-induced adenocarcinoma cells in primary culture. J. Steroid Chem. 13:29–37; 1980.
Llombart-Busch, A.; Peydro, A. Morphological, histochemical, and ultrastructural observations of diethylstilbestrol-induced kidney tumors in the Syrian golden hamster. Eur. J. Cancer 11:403–412; 1975.
Lund-Johansen, M.; Bjerkvig, R.; Anderson, K. J. Multicellular tumor spheroids in serum-free culture. Anticancer Res. 9:413–420; 1989.
Mathews, V. S.; Kirkman, H.; Bacon, R. L. Kidney damage in the golden hamster following chronic administration of diethylstilbestrol and sesame oil. Proc. Soc. Exp. Biol. Med. 66:195–196; 1947.
Oberley, T. D.; Lauchner, L. J.; Pugh, T. D., et al. Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media. Proc. Natl. Acad. Sci. USA 86:2107–2111; 1989.
Rosenberg, M. R.; Michalopoulous, G. Kidney proximal tubules isolated by collagenase perfusion grow in defined media in the absence of growth factors. J. Cell Physiol. 131:107–113; 1987.
Schwacofer, J. H.; Crooijmans, R. P.; Broers, J. L., et al. Multicellular aggregates from human tumor cell lines for radiation studies. Anticancer Res. 9:441–448; 1989.
Sirbasku, D. A.; Kirkland, W. L. Control of cell growth. IV. Growth properties of a new cell line established from an estrogen-dependent kidney tumor of the Syrian hamster. Endocrinology 98:1260–1272; 1976.
Talley, D. J.; Roy, W. A.; Li, J. J. Behavior of primary and serially transplanted estrogen-dependent renal carcinoma cells in monolayer and in collagen gel culture. In Vitro Cell. Dev. Biol. 18:149–156; 1982.
Walenta, S.; Bredel, A.; Karbach, U., et al. Interrelationship among morphology, metabolism, and proliferation of tumor cells in monolayer and spheroid culture. Adv. Exp. Med. Biol. 248:847–853; 1989.
West, C. M. Size-dependent resistance of human tumour spheroids to photodynamic treatment. Br. J. Cancer 59:510–514; 1989.
Westweber, D.; Kemler, R.; Ekblom, P. Cell adhesion molecule uvomorulin during kidney development. Dev. Biol. 112:213–221; 1985.
Yang, A. H.; Gould-Kostka, J.; Oberley, T. D. In vitro growth and differentiation of human kidney tubular cells on a basement membrane substrate. In Vitro Cell. Dev. Biol. 23:34–46; 1987.
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This study was supported by the Medical Research Service, Department of Veterans Affairs, Washington, DC, and by grant CA-22008 from the National Cancer Institute, NIH, DHHS, Bethesda, MD.
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Gonzalez, A., Oberley, T.D., Schultz, J.L. et al. In vitro characterization of estrogen induced syrian hamster renal tumors: Comparison with an immortalized cell line derived from diethylstilbestrol-treated adult hamster kidney. In Vitro Cell Dev Biol - Animal 29, 562–573 (1993). https://doi.org/10.1007/BF02634150
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DOI: https://doi.org/10.1007/BF02634150