@article{b1132869f6154a90b3055df6bed32c3e,
title = "Characterization of tumor-associated macrophages in prostate cancer transgenic mouse models",
abstract = "Background: Tumor-associated macrophages (TAMs) are critical components of the tumor microenvironment (TME) in prostate cancer. Commonly used orthotopic models do not accurately reflect the complete TME of a human patient or the natural initiation and progression of a tumor. Therefore, genetically engineered mouse models are essential for studying the TME as well as advancing TAM-targeted therapies. Two common transgenic (TG) models of prostate cancer are Hi-Myc and transgenic adenocarcinoma of the mouse prostate (TRAMP), but the TME and TAM characteristics of these models have not been well characterized. Methods: To advance the Hi-Myc and TRAMP models as tools for TAM studies, macrophage infiltration and characteristics were assessed using histopathologic, flow cytometric, and expression analyses in these models at various timepoints during tumor development and progression. Results: In both Hi-Myc and TRAMP models, macrophages adopt a more pro-tumor phenotype in higher histological grade tumors and in older prostate tissue. However, the Hi-Myc and TRAMP prostates differ in their macrophage density, with Hi-Myc tumors exhibiting increased macrophage density and TRAMP tumors exhibiting decreased macrophage density compared to age-matched wild type mice. Conclusions: The macrophage density and the adenocarcinoma cancer subtype of Hi-Myc appear to better mirror patient tumors, suggesting that the Hi-Myc model is the more appropriate in vivo TG model for studying TAMs and TME-targeted therapies.",
keywords = "Hi-Myc, TAM, TRAMP, pro-tumor, tumor microenvironment",
author = "{de Groot}, {Amber E.} and Myers, {Kayla V.} and Krueger, {Timothy E.G.} and Kiemen, {Ashley L.} and Nagy, {Natalia H.} and Alexandria Brame and Torres, {Vicente E.} and Zhongyuan Zhang and Levent Trabzonlu and Brennen, {W. Nathaniel} and Denis Wirtz and {De Marzo}, {Angelo M.} and Amend, {Sarah R.} and Pienta, {Kenneth J.}",
note = "Funding Information: The authors thank the members of the Johns Hopkins Urology Department, the Johns Hopkins Oncology Department, and the Pienta Lab, especially Kenneth C. Valkenburg, for training and thoughtful discussion. This work was supported by US Department of Defense CDMRP/PCRP (W81XWH‐17‐1‐0528) for W.N. Brennen; NCI SPORE grant in Prostate Cancer P50CA58236 and the NCI U01CA196390 for the Molecular and Cellular Characterization of Screen Detected Lesions (MCL) for A.M. De Marzo; US Department of Defense CDMRP/PCRP (W81XWH‐20‐1‐0353), the Patrick C. Walsh Prostate Cancer Research Fund, and the Prostate Cancer Foundation to S.R. Amend; NCI grants U54CA143803, CA163124, CA093900, and CA143055, and the Prostate Cancer Foundation to K.J. Pienta. This work was also supported by the William and Carolyn Stutt Research Fund, Ronald Rose, MC Dean, Inc., William and Marjorie Springer, Mary and Dave Stevens, Louis Dorfman, the Jones Family Foundation, Timothy Hanson, and the David and June Trone Family Foundation. Funding Information: The authors thank the members of the Johns Hopkins Urology Department, the Johns Hopkins Oncology Department, and the Pienta Lab, especially Kenneth C. Valkenburg, for training and thoughtful discussion. This work was supported by US Department of Defense CDMRP/PCRP (W81XWH-17-1-0528) for W.N. Brennen; NCI SPORE grant in Prostate Cancer P50CA58236 and the NCI U01CA196390 for the Molecular and Cellular Characterization of Screen Detected Lesions (MCL) for A.M. De Marzo; US Department of Defense CDMRP/PCRP (W81XWH-20-1-0353), the Patrick C. Walsh Prostate Cancer Research Fund, and the Prostate Cancer Foundation to S.R. Amend; NCI grants U54CA143803, CA163124, CA093900, and CA143055, and the Prostate Cancer Foundation to K.J. Pienta. This work was also supported by the William and Carolyn Stutt Research Fund, Ronald Rose, MC Dean, Inc., William and Marjorie Springer, Mary and Dave Stevens, Louis Dorfman, the Jones Family Foundation, Timothy Hanson, and the David and June Trone Family Foundation. Publisher Copyright: {\textcopyright} 2021 The Authors. The Prostate published by Wiley Periodicals LLC",
year = "2021",
month = jul,
day = "1",
doi = "10.1002/pros.24139",
language = "English (US)",
volume = "81",
pages = "629--647",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "10",
}