CXCL5 Facilitates Melanoma Cell-Neutrophil Interaction and Lymph Node Metastasis

The Journal of Investigative Dermatology
Ana Soler-CardonaRobert Loewe

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.

Citations

Dec 1, 2019·Experimental Dermatology·Julia Escandon Brehm, Barbara Bedogni
Oct 16, 2018·Frontiers in Immunology·Katharina Helene SusekAndreas Lundqvist
Apr 10, 2019·Endocrine-related Cancer·Kensey BergdorfVivian L Weiss
Mar 23, 2019·Frontiers in Immunology·Andrew O Yam, Tatyana Chtanova
May 1, 2020·Cell Death Discovery·Christine Brostjan, Rudolf Oehler
Feb 6, 2020·The Journal of Clinical Investigation·Balamayoora TheivanthiranBrent A Hanks
May 21, 2019·Frontiers in Immunology·Rae H FarnsworthSteven A Stacker
Feb 3, 2019·Cancer Research·Tara KarnezisSteven A Stacker
Feb 16, 2021·Frontiers in Oncology·Jia-An ZhangKun Chen
Feb 11, 2021·Cell Death Discovery·Christine Brostjan, Rudolf Oehler
Nov 27, 2021·Pigment Cell & Melanoma Research·John DaviesJulia A Newton-Bishop

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