Disruption of CCL20-CCR6 interaction inhibits metastasis of advanced cutaneous T-cell lymphoma

Oncotarget
S IkedaH Tagawa

Abstract

We recently demonstrated that upregulation of a chemokine receptor CCR6 and its ligand CCL20 led to metastasis of advanced cutaneous T-cell lymphoma (CTCL) cells, suggesting the involvement of CCL20-CCR6 interaction in initiating CTCL cell metastasis. In this study, we determined whether this interaction is functional in metastatic CTCL cells. We first demonstrated increased STAT3 expression during the progression of primary CTCL. STAT3 was spontaneously activated and mediated the transcription of CCL20 in CTCL cell lines. Next, to determine whether the transient knockdown of STAT3, CCL20, or CCR6 or treatment with neutralizing antibody against CCL20 (neutralizing CCL20 antibody) could reduce the migration ability of CTCL cells, we conducted an in vitro migration assay. All treatments reduced the nutrition-dependent migration activity of CTCL cells. Notably, treatment with neutralizing CCL20 antibody reduced the migration ability of the cells without decreasing the expression of CCL20 and CCR6. This demonstrated that the CCL20-CCR6 interaction is actually functional in metastatic CTCL cells. Finally, to examine the in vivo effect of neutralizing CCL20 antibody, we used NOD/Shi-scid IL-2γnul mice inoculated with CTCL cells. Thes...Continue Reading

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Citations

Jun 23, 2016·Oncotarget·Lise M LindahlNiels Odum
Apr 5, 2019·Oncology Letters·Cristiana TanaseRadu Albulescu
Oct 9, 2016·Seminars in Immunopathology·Thorbjørn KrejsgaardNiels Odum
Aug 20, 2016·F1000Research·Nooshin Bagherani, Bruce R Smoller
Dec 29, 2018·International Journal of Molecular Sciences·Elisabetta MarcuzziBianca Calì
Feb 24, 2016·International Journal of Molecular Sciences·Kyung Eun KimDaeho Cho
Jul 14, 2018·Medicines·Ranmali Ranasinghe, Rajaraman Eri

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Methods Mentioned

BETA
ELISA
FCS
transfection
PCR
Assay

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