CCL20 Expression by Tumor-Associated Macrophages Predicts Progression of Human Primary Cutaneous Melanoma
| Autor: | Paloma Sánchez-Mateos, Sandra Sánchez-Gregorio, Jorge García-Giménez, José Antonio Avilés, Rafael Samaniego, Enrique Mercader, Iván Márquez-Rodas, Alejandra Gutiérrez-González, Miguel Relloso, Alba Gutiérrez-Seijo |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Stromal cell Skin Neoplasms Immunology chemical and pharmacologic phenomena C-C chemokine receptor type 6 Metastasis 03 medical and health sciences Mice 0302 clinical medicine Cell Movement Medicine Animals Humans Melanoma Cells Cultured Cell Proliferation Chemokine CCL20 business.industry Macrophages Cancer hemic and immune systems respiratory system medicine.disease CCL20 030104 developmental biology 030220 oncology & carcinogenesis Cutaneous melanoma Cancer research Disease Progression Tumor necrosis factor alpha business |
| Zdroj: | Cancer immunology research. 6(3) |
| ISSN: | 2326-6074 |
| Popis: | The chemokine axis CCR6/CCL20 is involved in cancer progression in a variety of tumors. Here, we show that CCR6 is expressed by melanoma cells. The CCR6 ligand, CCL20, induces migration and proliferation in vitro, and enhances tumor growth and metastasis in vivo. Confocal analysis of melanoma tissues showed that CCR6 is expressed by tumor cells, whereas CCL20 is preferentially expressed by nontumoral cells in the stroma of certain tumors. Stromal CCL20, but not tumoral CCR6, predicted poor survival in a cohort of 40 primary melanoma patients. Tumor-associated macrophages (TAM), independently of their M1/M2 polarization profile, were identified as the main source of CCL20 in primary melanomas that developed metastasis. In addition to CCL20, TAMs expressed TNF and VEGF-A protumoral cytokines, suggesting that melanoma progression is supported by macrophages with a differential activation state. Our data highlight the synergistic interaction between melanoma tumor cells and prometastatic macrophages through a CCR6/CCL20 paracrine loop. Stromal levels of CCL20 in primary melanomas may be a clinically useful marker for assessing patient risk, making treatment decisions, and planning or analyzing clinical trials. Cancer Immunol Res; 6(3); 267–75. ©2018 AACR. |
| Databáze: | OpenAIRE |
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