Chemokine-mediated migration of melanoma cells towards lymphatics - a mechanism contributing to metastasis

JD Shields, MS Emmett, DBA Dunn, KD Joory, LM Sage, HS Rigby, PS Mortimer, A Orlando, JR Levick, DO Bates

Research output: Contribution to journalArticle (Academic Journal)peer-review

119 Citations (Scopus)

Abstract

The mechanisms that cause tumors such as melanomas to metastasize into peripheral lymphatic capillaries are poorly defined. Non-mutually-exclusive mechanisms are lymphatic endothelial cell (LEC) chemotaxis and proliferation in response to tumor cells (chemotaxis-lymphangiogenesis hypothesis) or LECs may secrete chemotactic agents that attract cancer cells (chemotactic metastasis hypothesis). Using migration assays, we found evidence supporting both hypotheses. Conditioned medium (CM) from metastatic malignant melanoma (MMM) cell lines attracted LEC migration, consistent with the lymphangiogenesis hypothesis. Conversely, CM from mixed endothelial cells or LECs, but not blood endothelial cells, attracted MMM cells but not non-metastatic melanoma cells, consistent with the chemotactic metastasis hypothesis. MMM cell lines expressed CCR7 receptors for the lymphatic chemokine CCL21 and CCL21 neutralizing antibodies prevented MMM chemotaxis in vitro. To test for chemotactic metastasis in vivo tumor cells were xenotransplanted into nude mice approximately 1 cm from an injected LEC depot. Two different MMM grew directionally towards the LECs, whereas non-metastatic melanomas did not. These observations support the hypothesis that MMM cells grow towards regions of high LEC density owing to chemotactic LEC secretions, including CCL21. This chemotactic metastasis may contribute to the close association between metastasizing tumor cells and peri-tumor lymphatic density and promote lymphatic invasion. PMID: 17130836 [PubMed - as supplied by publisher]
Translated title of the contributionChemokine-mediated migration of melanoma cells towards lymphatics - a mechanism contributing to metastasis
Original languageEnglish
Pages (from-to)2997 - 3005
Number of pages9
JournalOncogene
Volume26 (21)
DOIs
Publication statusPublished - May 2007

Bibliographical note

Publisher: Nature Publishing Group
Other: published online 27/11/06

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