Cargando…

Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production

Ambient temperature can regulate the immune response and affect tumor growth. Although thermoneutral caging reduces tumor growth via immune activation, little attention has been paid to the tumorigenic effect of low temperature. In the present study, tumor growth was higher at low ambient temperatur...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Eun-Ji, Chung, Tae-Wook, Kim, Keuk-Jun, Bae, Boram, Kim, Bo-Sung, Kim, Suhkmann, Ryu, Dongryeol, Bae, Sung-Jin, Ha, Ki-Tae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600495/
https://www.ncbi.nlm.nih.gov/pubmed/32993179
http://dx.doi.org/10.3390/biomedicines8100381
_version_ 1783603158101000192
author Lee, Eun-Ji
Chung, Tae-Wook
Kim, Keuk-Jun
Bae, Boram
Kim, Bo-Sung
Kim, Suhkmann
Ryu, Dongryeol
Bae, Sung-Jin
Ha, Ki-Tae
author_facet Lee, Eun-Ji
Chung, Tae-Wook
Kim, Keuk-Jun
Bae, Boram
Kim, Bo-Sung
Kim, Suhkmann
Ryu, Dongryeol
Bae, Sung-Jin
Ha, Ki-Tae
author_sort Lee, Eun-Ji
collection PubMed
description Ambient temperature can regulate the immune response and affect tumor growth. Although thermoneutral caging reduces tumor growth via immune activation, little attention has been paid to the tumorigenic effect of low temperature. In the present study, tumor growth was higher at low ambient temperature (4 °C for 8 h/d) than at the standard housing temperature (22 °C) in allograft models. Low temperature-stimulated tumor growth in mice was reduced by monocyte depletion using clodronate liposomes. Proliferation was considerably greater in cancer cells treated with 33 °C-cultured RAW264.7 cell-conditioned media (33CM) than in cells treated with 37 °C-cultured RAW264.7 cell-conditioned media (37CM). Additionally, glutamine levels were markedly higher in 33CM-treated cells than in 37CM-treated cells. We further confirmed that the addition of glutamine into 37CM enhanced its effects on cancer cell proliferation and glutamine uptake inhibition ameliorated the accelerated proliferation induced by 33CM. Consistently, the inhibition of glutamine uptake in the allograft model exposed to low temperature, effectively reduced tumor volume and weight. Collectively, these data suggest that the secretion and utilization of glutamine by macrophages and cancer cells, respectively, are key regulators of low temperature-enhanced cancer progression in the tumor microenvironment.
format Online
Article
Text
id pubmed-7600495
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76004952020-11-01 Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production Lee, Eun-Ji Chung, Tae-Wook Kim, Keuk-Jun Bae, Boram Kim, Bo-Sung Kim, Suhkmann Ryu, Dongryeol Bae, Sung-Jin Ha, Ki-Tae Biomedicines Article Ambient temperature can regulate the immune response and affect tumor growth. Although thermoneutral caging reduces tumor growth via immune activation, little attention has been paid to the tumorigenic effect of low temperature. In the present study, tumor growth was higher at low ambient temperature (4 °C for 8 h/d) than at the standard housing temperature (22 °C) in allograft models. Low temperature-stimulated tumor growth in mice was reduced by monocyte depletion using clodronate liposomes. Proliferation was considerably greater in cancer cells treated with 33 °C-cultured RAW264.7 cell-conditioned media (33CM) than in cells treated with 37 °C-cultured RAW264.7 cell-conditioned media (37CM). Additionally, glutamine levels were markedly higher in 33CM-treated cells than in 37CM-treated cells. We further confirmed that the addition of glutamine into 37CM enhanced its effects on cancer cell proliferation and glutamine uptake inhibition ameliorated the accelerated proliferation induced by 33CM. Consistently, the inhibition of glutamine uptake in the allograft model exposed to low temperature, effectively reduced tumor volume and weight. Collectively, these data suggest that the secretion and utilization of glutamine by macrophages and cancer cells, respectively, are key regulators of low temperature-enhanced cancer progression in the tumor microenvironment. MDPI 2020-09-26 /pmc/articles/PMC7600495/ /pubmed/32993179 http://dx.doi.org/10.3390/biomedicines8100381 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Eun-Ji
Chung, Tae-Wook
Kim, Keuk-Jun
Bae, Boram
Kim, Bo-Sung
Kim, Suhkmann
Ryu, Dongryeol
Bae, Sung-Jin
Ha, Ki-Tae
Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production
title Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production
title_full Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production
title_fullStr Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production
title_full_unstemmed Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production
title_short Macrophage Stimulated by Low Ambient Temperature Hasten Tumor Growth via Glutamine Production
title_sort macrophage stimulated by low ambient temperature hasten tumor growth via glutamine production
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600495/
https://www.ncbi.nlm.nih.gov/pubmed/32993179
http://dx.doi.org/10.3390/biomedicines8100381
work_keys_str_mv AT leeeunji macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT chungtaewook macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT kimkeukjun macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT baeboram macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT kimbosung macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT kimsuhkmann macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT ryudongryeol macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT baesungjin macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction
AT hakitae macrophagestimulatedbylowambienttemperaturehastentumorgrowthviaglutamineproduction