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J Invest Dermatol. 2018 Jul;138(7):1627-1635. doi: 10.1016/j.jid.2018.01.035. Epub 2018 Feb 21.

CXCL5 Facilitates Melanoma Cell-Neutrophil Interaction and Lymph Node Metastasis.

Author information

1
Skin and Endothelium Research Division, Department of Dermatology, Medical University of Vienna, Vienna, Austria; Division of General Dermatology and Dermato-Oncology, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
2
Skin and Endothelium Research Division, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
3
Institute of Molecular Biology GmbH, Mainz, Germany.
4
Department of Surgery, Medical University of Vienna, Vienna, Austria.
5
Core Facility Imaging, Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria.
6
Division of General Dermatology and Dermato-Oncology, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
7
Genes, Development and Disease Group, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
8
Skin and Endothelium Research Division, Department of Dermatology, Medical University of Vienna, Vienna, Austria; Division of General Dermatology and Dermato-Oncology, Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: robert.loewe@meduniwien.ac.at.

Abstract

Chemokines influence tumor metastasis by targeting tumor, stromal, and hematopoietic cells. Characterizing the chemokine mRNA expression profile of human primary melanoma samples, we found CXCL5 significantly up-regulated in stage T4 primary melanomas when compared to thin melanomas (T1 stage). To characterize the role of CXCL5 in melanoma progression, we established a metastasizing murine xenograft model using CXCL5-overexpressing human melanoma cells. CXCL5 had no effect on melanoma proliferation in vitro and on primary tumor growth in vivo, but CXCL5-overexpressing tumors recruited high amounts of neutrophils and exhibited significantly increased lymphangiogenesis in our severe combined immune-deficient mouse model. Recruited neutrophils were found in close proximity to or within lymphatic vessels, often in direct contact with melanoma cells. Clinically, CXCL5-overexpressing melanomas had significantly increased lymph node metastases. We were able to translate these findings to human patient samples and found a positive correlation between CXCL5 expression, numbers of neutrophils in stage T4 primary melanoma, and the occurrence of subsequent locoregional metastasis.

PMID:
29474942
DOI:
10.1016/j.jid.2018.01.035

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