Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas
Chronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tum...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00587/full |
| _version_ | 1811238890376265728 |
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| author | Jason M. Fritz Meredith A. Tennis David J. Orlicky Hao eYin Cynthia eJu Elizabeth F. Redente Kevin S. Choo Taylor A. Staab Ronald J. Bouchard Daniel T. Merrick Alvin M. Malkinson Lori` D. Dwyer-Nield |
| author_facet | Jason M. Fritz Meredith A. Tennis David J. Orlicky Hao eYin Cynthia eJu Elizabeth F. Redente Kevin S. Choo Taylor A. Staab Ronald J. Bouchard Daniel T. Merrick Alvin M. Malkinson Lori` D. Dwyer-Nield |
| author_sort | Jason M. Fritz |
| collection | DOAJ |
| description | Chronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programming changes within 2 weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ≤ 50% of control levels after 4-6 weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of IGF-I, CXCL1, IL-6 and CCL2 diminished with clodronate liposome treatment. Tumor associated macrophages expressed markers of both M1 and M2 programming in vehicle and clodronate liposome treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2) had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression. |
| first_indexed | 2024-04-12T12:50:10Z |
| format | Article |
| id | doaj.art-1962a59ee4504d73968833dd92f71b02 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T12:50:10Z |
| publishDate | 2014-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1962a59ee4504d73968833dd92f71b022022-12-22T03:32:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-11-01510.3389/fimmu.2014.00587101900Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomasJason M. Fritz0Meredith A. Tennis1David J. Orlicky2Hao eYin3Cynthia eJu4Elizabeth F. Redente5Kevin S. Choo6Taylor A. Staab7Ronald J. Bouchard8Daniel T. Merrick9Alvin M. Malkinson10Lori` D. Dwyer-Nield11University of Colorado Anschutz Medical CenterUniversity of Colorado Anschutz Medical CenterUniversity of Colorado Anschutz Medical CenterUniversity of Colorado Anschutz Medical CenterUniversity of Colorado Anschutz Medical CenterNational Jewish HealthEastern Colorado Veterans Administration Medical CenterEastern Colorado Veterans Administration Medical CenterEastern Colorado Veterans Administration Medical CenterUniversity of Colorado Anschutz Medical CenterUniversity of Colorado Anschutz Medical CenterUniversity of Colorado Anschutz Medical CenterChronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programming changes within 2 weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ≤ 50% of control levels after 4-6 weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of IGF-I, CXCL1, IL-6 and CCL2 diminished with clodronate liposome treatment. Tumor associated macrophages expressed markers of both M1 and M2 programming in vehicle and clodronate liposome treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2) had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00587/fullTumor Microenvironmentlung cancermouse modelsmacrohpage depletionmacrophage programming |
| spellingShingle | Jason M. Fritz Meredith A. Tennis David J. Orlicky Hao eYin Cynthia eJu Elizabeth F. Redente Kevin S. Choo Taylor A. Staab Ronald J. Bouchard Daniel T. Merrick Alvin M. Malkinson Lori` D. Dwyer-Nield Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas Frontiers in Immunology Tumor Microenvironment lung cancer mouse models macrohpage depletion macrophage programming |
| title | Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas |
| title_full | Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas |
| title_fullStr | Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas |
| title_full_unstemmed | Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas |
| title_short | Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas |
| title_sort | depletion of tumor associated macrophages slows the growth of chemically induced mouse lung adenocarcinomas |
| topic | Tumor Microenvironment lung cancer mouse models macrohpage depletion macrophage programming |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00587/full |
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