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6. Embryonal mass and hormone-associated effects of pregnancy inducing a differential growth of four murine tumors

Author

Bustuoabad, Oscar David, di Gianni, Pedro D., Franco, Marcela, Kordon, Edith Claudia, Vanzulli, Silvia I., Meiss, Roberto P., Grion, Lorena C., Diaz, Graciela Susana, Nosetto, Sergio H., Hockl, Pablo Francisco, Lombardi, María Gabriela, Pasqualini, Christiane Dosne, and Ruggiero, Raul Alejandro

Subjects
Male, CIENCIAS MÉDICAS Y DE LA SALUD, Fibrosarcoma, Indomethacin, Adenocarcinoma, HORMONE REGULATION, Mice, Pregnancy, MURINE TUMORS, Animals, Progesterone, Mice, Inbred BALB C, Neovascularization, Pathologic, LIF, Anti-Inflammatory Agents, Non-Steroidal, Teratoma, TNFa, Mammary Neoplasms, Experimental, Patología, Estrogens, Neoplasms, Experimental, purl.org/becyt/ford/3.1 [https], Bioquímica y Biología Molecular, Hormones, MAMMARY INVOLUTION, Leukemia, Lymphoid, Medicina Básica, ERK, PREGNANCY, Female, purl.org/becyt/ford/3 [https], Receptors, Progesterone, Pregnancy Complications, Neoplastic, Cell Division, Neoplasm Transplantation
Abstract

A differential effect of pregnancy on the growth of subcutaneous implants of four murine tumors has been observed. Two tumors lacking receptors for progesterone and estrogen [methylcholanthrene-induced fibrosarcoma (MC-C) and spontaneous lymphoid leukemia (LB)] exhibited slow kinetics throughout the course of pregnancy, although inhibition was stronger beyond day 10. On the other hand, one of two tumors bearing receptors for progesterone and estrogen [medroxyprogesterone (MPA)-induced mammary adenocarcinoma (C7HI)] exhibited three phases: up to days 8-10 of gestation the tumor grew faster than in virgins, between days 8-10 and 15 it reached a plateau, and beyond day 15 a sharp reduction in tumor mass was observed. The other tumor [mouse mammary tumor virus (MMTV)-induced mammary carcinoma(T2280)] behaved as a typical pregnancy-dependent tumor (i.e., it grew in pregnant but not in virgin mice, regressed soon after delivery, and reassumed its growth at the middle of a second round of pregnancy). Neither MPA nor estrogen affected MC-C and LB tumor growth. On the other hand, MPA-treated mice enhanced C7HI tumor and reciprocally C7HI tumor-bearing mice treated with estrogen strongly inhibited tumor growth. As for T2280, neither MPA nor estrogen alone could promote tumor growth and, in consequence, no tumor developed. However, when MPA plus estrogen was administered in a schedule simulating the successive appearance of these hormones in pregnancy, T2280 grew even faster than in pregnant mice. When the four tumors were implanted in mice bearing grafts of embryonal tissues (teratomas), all of them were inhibited. This antitumor effect was similar to that observed in pregnancy when tumors unresponsive to progesterone and estrogen were tested. On the other hand, with tumors bearing progesterone and estrogen receptors, differences in tumor growth were detected in pregnant and teratoma-bearing mice. This suggested the existence during pregnancy of two factors potentially acting on tumor growth. First, a progesterone and estrogen-mediated hormonal component, which would exert either inhibitory or stimulatory effects only evidenced with tumors bearing hormonal receptors. Secondly, an antitumor effect proportional to the growing embryonal mass, inhibiting all tumors independently of their origin or hormone responsiveness. This antitumor effect could be attributed to a beat-resistant serum factor (1,000-1,200 Da molecular weight) presumably associated with the pathway of the arachidonic acid metabolism. The interplay between the hormonal component and the serum factor associated with embryonal mass could account for some of the largely heterogeneous and otherwise unexplained effects of pregnancy on tumor growth reported in the literature and illustrated by the four tumors studied here. Fil: Bustuoabad, Oscar David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: di Gianni, Pedro D.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Franco, Marcela. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Vanzulli, Silvia I.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Grion, Lorena C.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Diaz, Graciela Susana. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Nosetto, Sergio H.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Hockl, Pablo Francisco. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Lombardi, María Gabriela. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Pasqualini, Christiane Dosne. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Ruggiero, Raul Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina

Published
2002

9. Effect of sialoadenectomy on medroxyprogesterone-acetate-induced mammary carcinogenesis in BALB/c mice. Correlation between histology and epidermal-growth-factor receptor content

Author

Kordon, Edith C., primary, Guerra, Fabiana, additional, Molinolo, Alfredo A., additional, Elizalde, Patricia, additional, Charreau, Eduardo H., additional, Pasqualini, Christiane Dosne, additional, Montecchia, Fernanda, additional, Pazos, Patricia, additional, Dran, Graciela, additional, and Lanari, Claudia, additional

Published
1994
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15. Priorizar la creatividad sobre el factor de impacto

Author

Pasqualini, Christiane Dosne and Pasqualini, Christiane Dosne

Subjects
Bibliometrics, Technical writing, Technical publishing, Technical editing
Abstract

Title from PDF cover (viewed Feb. 8, 2007).

Published
2003

31. Macrophages and Tumor Growth. II. Cell Kinetics at the Site of Allogeneic Tumor Growth

Author

Barrera, Clydes, Mazzolli, Alicia, Bustuoabad, Oscar, Andreetta, Maria, and Pasqualini, Christiane Dosne

Abstract

The sponge matrix allograft model made possible the growth of an AKR lymphoma in a certain percentage of BALB/c mice making progressors (tumor-bearing) and regressors (tumor-rejecting) simultaneously available. Mice bearing either an AKR kidney allograft or a sponge alone were used as controls. The cell population infiltrating the sponge was evaluated 2, 5, 10, 15, and 21 days after subcutaneous implantation. It consisted of macrophages, lymphocytes, and neutrophils. There was no difference between groups on Day 2 and Day 5. From Day 10 onwards, tumor growth was evident with a clear cut separation between progressors and regressors. The latter behaved like the two control groups except for a significant increase in lymphocytes on Day 21. The progressors showed a striking increase in total cell count from Day 10 onwards. Macrophages were the major population with a maximum value of 201 X 106 as compared to 8 X 106 in the regressors; their phagocytic and lysosomal activity remained similar in all groups. The lymphocytes showed no variation in absolute numbers but, because of the high cell count in progressors, their ratio to macrophages reached 1:50 on Day 10, making up only 2% of the cell population. Neutrophils were significantly increased in progressors as compared with the other groups. It can be concluded that in the presence of a foreign body reaction a marked influx of macrophages accompanies allogeneic tumor growth.

Published
1985
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