CXCL5 Facilitates Melanoma Cell-Neutrophil Interaction and Lymph Node Metastasis

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Cell Communication / immunology
  • Cell Line, Tumor
  • Chemokine CXCL5 / immunology
  • Chemokine CXCL5 / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphangiogenesis / immunology
  • Lymphatic Metastasis / immunology*
  • Lymphatic Metastasis / pathology
  • Melanoma / immunology
  • Melanoma / pathology*
  • Mice
  • Mice, Hairless
  • Mice, SCID
  • Neoplasm Staging
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • RNA, Messenger / metabolism
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology*
  • Specific Pathogen-Free Organisms
  • Spheroids, Cellular
  • Up-Regulation


  • Biomarkers, Tumor
  • CXCL5 protein, human
  • Chemokine CXCL5
  • RNA, Messenger