In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development
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 vi...
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todo:paper_10780432_v23_n17_p5135_Jaworski2023-10-03T16:03:37Z In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development 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. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_10780432_v23_n17_p5135_Jaworski |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Jaworski, F.M. |
| title |
In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development |
| title_short |
In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development |
| title_full |
In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development |
| title_fullStr |
In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development |
| title_full_unstemmed |
In vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development |
| title_sort |
in vivo hemin conditioning targets the vascular and immunologic compartments and restrains prostate tumor development |
| url |
http://hdl.handle.net/20.500.12110/paper_10780432_v23_n17_p5135_Jaworski |
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