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FCM - Instituto de Genética Experimental

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https://rephip.unr.edu.ar/handle/2133/1908

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Examinando FCM - Instituto de Genética Experimental por Autor "Bonfil, R. Daniel"

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  • Miniatura
    ÍtemAcceso Abierto
    Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells
    (Wiley, 2002-05-02) Binda, María Mercedes; Matar, Pablo; González, Alejandro D.; Rozados, Viviana R.; Gervasoni, Silvia I.; Scharovsky, O. Graciela; Bonfil, R. Daniel
    The phenomenon by which tumor-bearing hosts are capable of inhibiting secondary tumor implants or metastases, known as concomitant antitumoral resistance (CAR), is presumably due to antiangiogenesis at places distant from the primary tumor. Although angiostatin, a potent inhibitor of angiogenesis, has been reported to be one of the factors responsible for suppressing the growth of secondary tumors in mice bearing previous tumors, it has not been definitively proven yet. With the aim of investigating whether CAR-inducing cancer cells display a differential angiostatin production and to support the role ascribed to that molecule concerning the inhibition of secondary tumor implants, 5 tumor models with different CAR-inducing capacities were studied herein. One of the 2 human lung cancer cell lines analyzed revealed a strong CAR against secondary s.c. tumor implants in nude mice, and 2 of 3 of the murine mammary tumors used exhibited inhibitory effect on secondary s.c. and i.v. tumor inoculations in syngeneic hosts. Since angiostatin is a proteolytic fragment from plasminogen, we examined by Western blot the ability of all conditioned media collected from the tumor cells studied to convert plasminogen to angiostatin. An association between in vivo generation of CAR and in vitro conversion of plasminogen into angiostatin was found. Since different enzymatic mechanisms were described to explain the generation of angiostatin, we also studied gelatinase and urokinase-type plasminogen activator secretion in conditioned media by zymography. The conversion of plasminogen into angiostatin by conditioned media was mainly inhibited by broad-spectrum serine proteinase inhibitors, suggesting a possible role for 1 or more enzymes of that group in the process. These findings suggest the existence of a differential angiostatin generation by CAR-inducing cancer cells, providing additional support to previous data obtained by other authors.
  • Miniatura
    ÍtemAcceso Abierto
    Paradoxical antiproliferative effect by a murine mammary tumor-derived epithelial cell line
    (BioMed Central, 2007-10-01) Gurzov, Esteban N.; Nabha, Sanaa M.; Yamamoto, Hamilto; Meng, Hong; Scharovsky, O. Graciela; Bonfil, R. Daniel
    Background Despite significant advancement in breast cancer therapy, there is a great need for a better understanding of the mechanisms involved in breast carcinogenesis and progression, as well as of the role of epigenetic contributions from stromal cells in mammary tumorigenesis. In this study, we isolated and characterized murine mammary tumor-derived epithelial and myofibroblast cell lines, and investigated the in vitro and in vivo effect of cellular soluble factors produced by the epithelial cell line on tumor cells. Methods Morphology, immunophenotype, cytogenetics, invasiveness, and tumorigenicity of epithelial (LM-234ep) and myofibroblast (LM-234mf) cell lines isolated from two murine mammary adenocarcinomas with common ancestor were studied. The in vitro effects of LM-234ep conditioned medium on proliferation, cell cycle distribution, and expression of cell cycle proteins, were investigated in LM-234mf cells, mouse melanoma cells (B16-F10), and human cervical adenocarcinoma cells (HeLa). The in vivo anti-tumor activity of LM-234ep conditioned media was evaluated in subcutaneous tumors formed in nude mice by B16-F10 and HeLa cells. Results LM-234ep cells were found to be cytokeratin positive and hipertriploid, whereas LM-234mf cells were α-smooth muscle actin positive and hypohexaploid. Chromosome aberrations were found in both cases. Only LM-234mf revealed to be invasive in vitro and to secrete active MMP-2, though neither of the cell types were able to produce progressing tumors. LM-234ep-derived factors were able to inhibit the in vitro growth of LM-234mf, B16-F10, and HeLa cells, inducing cell cycle arrest in G0/G1 phase. The administration of LM-234ep conditioned medium inhibited the growth of B16-F10 and HeLa tumors in nude mice. Conclusion Our data suggest the existence of epithelial cell variants with tumor suppressive properties within mammary tumors. To our knowledge, this is the first report showing antiproliferative and antineoplastic activities induced by tumor-derived epithelial cells.