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Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation.

作者信息

Tham Muly, Tan Kar Wai, Keeble Jo, Wang Xiaojie, Hubert Sandra, Barron Luke, Tan Nguan Soon, Kato Masashi, Prevost-Blondel Armelle, Angeli Veronique, Abastado Jean-Pierre

机构信息

Singapore Immunology Network, BMSI, A-STAR, Singapore.

Singapore Immunology Network, BMSI, A-STAR, Singapore. Department of Clinical Research, Singapore General Hospital, Singapore.

出版信息

Oncotarget. 2014 Dec 15;5(23):12027-42. doi: 10.18632/oncotarget.2482.

DOI:10.18632/oncotarget.2482
PMID:25294815
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4322977/
Abstract

M2 macrophages promote tumor growth and metastasis, but their interactions with specific tumor cell populations are poorly characterized. Using a mouse model of spontaneous melanoma, we showed that CD34- but not CD34+ tumor-initiating cells (TICs) depend on M2 macrophages for survival and proliferation. Tumor-associated macrophages (TAMs) and macrophage-conditioned media protected CD34- TICs from chemotherapy in vitro. In vivo, while inhibition of CD115 suppressed the macrophage-dependent CD34- TIC population, chemotherapy accelerated its development. The ability of TICs to respond to TAMs was acquired during melanoma progression and immediately preceded a surge in metastatic outgrowth. TAM-derived transforming growth factor-β (TGFβ) and polyamines produced via the Arginase pathway were critical for stimulation of TICs and synergized to promote their growth.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/cf127b910242/oncotarget-05-12027-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/ea2b7d3becee/oncotarget-05-12027-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/2066e534f13c/oncotarget-05-12027-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/c41d477010cf/oncotarget-05-12027-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/c89a1b5155e2/oncotarget-05-12027-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/87be60d7efc9/oncotarget-05-12027-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/ea39c402ceeb/oncotarget-05-12027-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/593292df54aa/oncotarget-05-12027-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/cf127b910242/oncotarget-05-12027-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/ea2b7d3becee/oncotarget-05-12027-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/2066e534f13c/oncotarget-05-12027-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/c41d477010cf/oncotarget-05-12027-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/c89a1b5155e2/oncotarget-05-12027-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/87be60d7efc9/oncotarget-05-12027-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/ea39c402ceeb/oncotarget-05-12027-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/593292df54aa/oncotarget-05-12027-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81f/4322977/cf127b910242/oncotarget-05-12027-g008.jpg

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引用本文的文献

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Mannose-functionalization of reconstituted high-density lipoprotein nanoparticles improves payload delivery and enhances M2-to-M1 phenotype reprogramming of RAW 264.7 macrophages polarized by B16-F10 melanoma cells.

Front Drug Deliv. 2023-10-24

[2]
Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.

Mol Cancer. 2025-5-21

[3]
Macrophages in inflammatory skin diseases and skin tumors.

Front Immunol. 2024-12-5

[4]
Targeting cancer metabolic pathways for improving chemotherapy and immunotherapy.

Cancer Lett. 2023-10-28

[5]
Macrophage's role in solid tumors: two edges of a sword.

Cancer Cell Int. 2023-7-31

[6]
Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application .

Nanomaterials (Basel). 2023-1-17

[7]
The protective effect of the TSPO ligands 2,4-Di-Cl-MGV-1, CB86, and CB204 against LPS-induced M1 pro-inflammatory activation of microglia.

Brain Behav Immun Health. 2020-5-21

[8]
Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer.

Front Cell Dev Biol. 2021-5-20

[9]
Characteristics of the Tumor Microenvironment That Influence Immune Cell Functions: Hypoxia, Oxidative Stress, Metabolic Alterations.

Cancers (Basel). 2020-12-17

[10]
Correlation of tumor-infiltrating immune cells of melanoma with overall survival by immunogenomic analysis.

Cancer Med. 2020-11

本文引用的文献

[1]
CSF-1R inhibition alters macrophage polarization and blocks glioma progression.

Nat Med. 2013-9-22

[2]
SMAD3 deficiency promotes inflammatory aortic aneurysms in angiotensin II-infused mice via activation of iNOS.

J Am Heart Assoc. 2013-6-19

[3]
Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention.

Amino Acids. 2013-6-15

[4]
The in-vitro spheroid culture induces a more highly differentiated but tumorigenic population from melanoma cell lines.

Melanoma Res. 2013-8

[5]
Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression.

Oncogene. 2013-6-3

[6]
Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden.

Mol Cancer. 2013-3-27

[7]
Role of macrophage targeting in the antitumor activity of trabectedin.

Cancer Cell. 2013-2-11

[8]
TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer.

J Clin Invest. 2013-2-8

[9]
Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses.

Cancer Res. 2012-12-5

[10]
The harmonies played by TGF-β in stem cell biology.

Cell Stem Cell. 2012-12-7

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