Tumor-derived CCL20 affects B16 melanoma growth in mice

• Verfasst von: Martín-García, Diego [VerfasserIn]
• Verfasst von: Silva-Vilches, Cinthia [VerfasserIn]
• Verfasst von: Will, Rainer D. [VerfasserIn]
• Verfasst von: Enk, Alexander [VerfasserIn]
• Verfasst von: Lonsdorf, Anke Susanne [VerfasserIn]
• Titel: Tumor-derived CCL20 affects B16 melanoma growth in mice
• Verf.angabe: Diego Martin-Garcia, Cinthia Silva-Vilches, Rainer Will, Alexander H. Enk, Anke S. Lonsdorf
• Jahr: 2020
• Jahr des Originals: 2019
• Fussnoten: Accepted 8 December 2019 ; Gesehen am 07.04.2020
• Titel Quelle: Enthalten in: Journal of dermatological science
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1990
• Jahr Quelle: 2020
• Band/Heft Quelle: 97(2020), 1, Seite 57-65$79
• ISSN Quelle: 1873-569X
• DOI: doi:10.1016/j.jdermsci.2019.12.005
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CCL20
• Sach-SW: CCR6
• Sach-SW: Chemokines
• Sach-SW: Melanoma
• Sach-SW: Tumor infiltrating leucocytes
• K10plus-PPN: 1694194671

Abstract

Background - Chemokine ligand-20 (CCL20) expressed in the epidermis is a potent impetus for the recruitment of CC-chemokine receptor 6 (CCR6)-expressing subsets of DCs, B-cells and memory T-cells into the skin. CCL20 and CCR6+ immune cells have been detected in chronic inflammatory skin diseases and several malignancies, including melanoma. Yet, the functional contribution of the CCR6/CCL20 axis for melanoma progression remains controversial. - Objective - The functional contribution of CCR6-expressing immune cell subsets and local CCL20 in the tumor microenvironment for the immune control of melanoma was studied. - Methods - Homeostatic and inducible CCL20 secretion of murine (B16, Ret) and human (A375, C32) melanoma cells was analyzed by ELISA. To assess the functional relevance of CCR6/CCL20 interactions on local tumor progression, prestimulated or retrovirally transduced B16/F1 melanoma cells overexpressing CCL20 (B16-CCL20) were injected subcutaneously into C57BL/6 Wt mice and congenic CCR6-deficient (CCR6−/−) mice. Infiltrating leucocytes were examined by flow cytometry in tumors and draining lymph nodes (DLNs). - Results - Melanoma cell lines up-regulate CCL20 secretion upon stimulation with pro-inflammatory cytokines in vitro. While only moderate changes in phenotype and composition of leucocytes were detected in advanced tumors and DLNs, mice injected with CCR6+ B16-CCL20 cells developed smaller tumors compared to B16-Control injected littermates, with CCR6-/- mice displaying the most pronounced reduction in tumor growth and incidence. - Conclusion - Our results suggest that CCR6/CCL20 interactions and individual independent effects of CCL20 and CCR6 in the microenvironment may be essential for melanoma progression and suggest a decisive role of this chemokine axis for melanoma pathogenesis beyond chemoattraction.