Artículo

Jaworski, F.M.; Gentilini, L.D.; Gueron, G.; Meiss, R.P.; Ortiz, E.G.; Berguer, P.M.; Ahmed, A.; Navone, N.; Rabinovich, G.A.; Compagno, D.; Laderach, D.J.; Vazquez, E.S. "In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development" (2017) Clinical Cancer Research. 23(17):5135-5148
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Abstract:

Purpose: Conditioning strategies constitute a relatively unexplored and exciting opportunity to shape tumor fate by targeting the tumor microenvironment. In this study, we assessed how hemin, a pharmacologic inducer of heme oxygenase-1 (HO-1), has an impact on prostate cancer development in an in vivo conditioning model. Experimental Design: The stroma of C57BL/6 mice was conditioned by subcutaneous administration of hemin prior to TRAMP-C1 tumor challenge. Complementary in vitro and in vivo assays were performed to evaluate hemin effect on both angiogenesis and the immune response. To gain clinical insight, we used prostate cancer patient-derived samples in our studies to assess the expression of HO-1 and other relevant genes. Results: Conditioning resulted in increased tumor latency and decreased initial growth rate. Histologic analysis of tumors grown in conditioned mice revealed impaired vascularization. Hemin-treated human umbilical vein endothelial cells (HUVEC) exhibited decreased tubulogenesis in vitro only in the presence of TRAMP-C1-conditioned media. Subcutaneous hemin conditioning hindered tumor-associated neovascularization in an in vivo Matrigel plug assay. In addition, hemin boosted CD8+ T-cell proliferation and degranulation in vitro and antigen-specific cytotoxicity in vivo. A significant systemic increase in CD8+ T-cell frequency was observed in preconditioned tumor-bearing mice. Tumors from hemin-conditioned mice showed reduced expression of galectin-1 (Gal-1), key modulator of tumor angiogenesis and immunity, evidencing persistent remodeling of the microenvironment. We also found a subset of prostate cancer patient-derived xenografts and prostate cancer patient samples with mild HO-1 and low Gal-1 expression levels. Conclusions: These results highlight a novel function of a human-used drug as a means of boosting the antitumor response. © 2017 American Association for Cancer Research.

Registro:

Documento: Artículo
Título:In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development
Autor:Jaworski, F.M.; Gentilini, L.D.; Gueron, G.; Meiss, R.P.; Ortiz, E.G.; Berguer, P.M.; Ahmed, A.; Navone, N.; Rabinovich, G.A.; Compagno, D.; Laderach, D.J.; Vazquez, E.S.
Filiación:Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales (FCEN), Departamento de Química Biologica (QB), Laboratorio de Inflamacion y Cancer, Intendente Guiraldes 2160, Piso 4, Buenos Aires, Argentina
Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales (FCEN), Departamento de Química Biologica (QB), Laboratorio de Glico-Oncología Molecular y Funcional, Buenos Aires, Argentina
CONICET, Universidad de Buenos Aires (UBA), Instituto de Química Biologica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Intendente Guiraldes 2160, Pabellon II, Buenos Aires, 1428, Argentina
Department of Pathology, Institute of Oncological Studies, National Academy of Medicine, Buenos Aires, Argentina
Fundacion Instituto Leloir (FIL), IIBBA - CONICET, Buenos Aires, Argentina
Aston Medical Research Institute, Aston Medical School, University of Aston, Birmingham, United Kingdom
Department of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, University of Texas MD Anderson Cancer Center, Houston, TX, United States
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Departamento de Ciencias Basicas, Universidad Nacional de Lujan, Buenos Aires, Argentina
Palabras clave:galectin 1; heme oxygenase 1; hemin; galectin 1; heme oxygenase 1; hemin; angiogenesis; animal cell; animal experiment; animal model; animal tissue; antigen specificity; antineoplastic activity; Article; cancer inhibition; CD8+ T lymphocyte; controlled study; culture medium; cytotoxicity; degranulation; gene expression; histopathology; human; human tissue; immune response; immunosuppressive treatment; in vitro study; in vivo study; lymphocyte proliferation; male; model; mouse; neovascularization (pathology); nonhuman; priority journal; prostate tumor; tumor immunity; tumor microenvironment; tumor vascularization; tumor xenograft; umbilical vein endothelial cell; animal; antagonists and inhibitors; cell proliferation; disease model; drug effect; drug screening; gene expression regulation; genetics; neovascularization (pathology); pathology; prostate tumor; Animals; CD8-Positive T-Lymphocytes; Cell Proliferation; Disease Models, Animal; Galectin 1; Gene Expression Regulation, Neoplastic; Heme Oxygenase-1; Hemin; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Neovascularization, Pathologic; Prostatic Neoplasms; Xenograft Model Antitumor Assays
Año:2017
Volumen:23
Número:17
Página de inicio:5135
Página de fin:5148
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-17-0112
Título revista:Clinical Cancer Research
Título revista abreviado:Clin. Cancer Res.
ISSN:10780432
CODEN:CCREF
CAS:galectin 1, 258495-34-0; hemin, 16009-13-5; Galectin 1; Heme Oxygenase-1; Hemin
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10780432_v23_n17_p5135_Jaworski

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Citas:

---------- APA ----------
Jaworski, F.M., Gentilini, L.D., Gueron, G., Meiss, R.P., Ortiz, E.G., Berguer, P.M., Ahmed, A.,..., Vazquez, E.S. (2017) . In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development. Clinical Cancer Research, 23(17), 5135-5148.
http://dx.doi.org/10.1158/1078-0432.CCR-17-0112
---------- CHICAGO ----------
Jaworski, F.M., Gentilini, L.D., Gueron, G., Meiss, R.P., Ortiz, E.G., Berguer, P.M., et al. "In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development" . Clinical Cancer Research 23, no. 17 (2017) : 5135-5148.
http://dx.doi.org/10.1158/1078-0432.CCR-17-0112
---------- MLA ----------
Jaworski, F.M., Gentilini, L.D., Gueron, G., Meiss, R.P., Ortiz, E.G., Berguer, P.M., et al. "In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development" . Clinical Cancer Research, vol. 23, no. 17, 2017, pp. 5135-5148.
http://dx.doi.org/10.1158/1078-0432.CCR-17-0112
---------- VANCOUVER ----------
Jaworski, F.M., Gentilini, L.D., Gueron, G., Meiss, R.P., Ortiz, E.G., Berguer, P.M., et al. In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development. Clin. Cancer Res. 2017;23(17):5135-5148.
http://dx.doi.org/10.1158/1078-0432.CCR-17-0112