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Characterization of tumor‐associated macrophages in prostate cancer transgenic mouse models
Author(s) -
Groot Amber E.,
Myers Kayla V.,
Krueger Timothy E. G.,
Kiemen Ashley L.,
Nagy Natalia H.,
Brame Alexandria,
Torres Vicente E.,
Zhang Zhongyuan,
Trabzonlu Levent,
Brennen W. Nathaniel,
Wirtz Denis,
De Marzo Angelo M.,
Amend Sarah R.,
Pienta Kenneth J.
Publication year - 2021
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.24139
Subject(s) - tramp , prostate cancer , tumor microenvironment , prostate , adenocarcinoma , cancer research , macrophage , genetically modified mouse , tumor progression , medicine , cancer , transgene , pathology , biology , in vitro , gene , biochemistry
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.