CCL21 Chemokine Regulates Chemokine Receptor CCR7 Bearing Malignant Melanoma Cells

Hiroya Takeuchi, Akihide Fujimoto, Maki Tanaka, Tomoki Yamano, Eddy Hsueh, Dave S B Hoon

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Purpose: The chemokine CC-ligand 21/secondary lymphoid tissue chemokine (CCL21/SLC) regulates the homing of naïve T cells and dendritic cells that express CC-chemokine receptor 7 (CCR7) from distant sites to lymphoid tissue such as lymph nodes. We hypothesized that CCL21/SLC regulates the migration of CCR7-bearing melanoma cells from a primary lesion to regional tumor-draining lymph nodes. Experimental Design: Quantitative real-time reverse transcriptase-PCR (qRT) assay and immunohistochemistry (IHC) were used to assess the level of CCR7 expression in melanoma cell lines and in primary and metastatic melanoma tumors. Cell migration assay using melanoma cell lines was performed under the induction of CCL21/SLC. The CCL21/SLC expression level in tumor-draining sentinel lymph nodes (SLNs) was assessed by both qRT assay and IHC. Results: Melanoma cell lines and tumors demonstrated heterogeneous expression of CCR7 mRNA by qRT assay. There was strong functional correlation between CCR7 mRNA expression and cell migration induced by CCL21/SLC. IHC evidence of CCR7 expression in primary melanomas significantly (P = 0.02) correlated with Breslow thickness. Assessment of SLN from 55 melanoma patients by qRT assay demonstrated that CCL21/SLC mRNA expression level was significantly (P = 0.008) higher in pathologically melanoma-negative SLNs than in melanoma-positive SLNs. Conclusions: This report demonstrates a potential mechanism for recruitment and homing of CCR7(+) metastatic melanoma cells to tumor-draining lymph nodes, which express CCL21/SLC. The study also suggests that lymph nodes bearing metastasis may suppress CCL21/SLC production.

Original languageEnglish
Pages (from-to)2351-2358
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number7
DOIs
Publication statusPublished - 2004 Apr 1
Externally publishedYes

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CCR7 Receptors
Chemokine CCL21
Chemokine Receptors
CC Chemokines
Melanoma
Ligands
Reverse Transcriptase Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Lymph Nodes
Immunohistochemistry
Messenger RNA
Neoplasms
Cell Migration Assays
Cell Line
Lymphoid Tissue
Tumor Cell Line
Dendritic Cells
Cell Movement

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Takeuchi, H., Fujimoto, A., Tanaka, M., Yamano, T., Hsueh, E., & Hoon, D. S. B. (2004). CCL21 Chemokine Regulates Chemokine Receptor CCR7 Bearing Malignant Melanoma Cells. Clinical Cancer Research, 10(7), 2351-2358. https://doi.org/10.1158/1078-0432.CCR-03-0195

CCL21 Chemokine Regulates Chemokine Receptor CCR7 Bearing Malignant Melanoma Cells. / Takeuchi, Hiroya; Fujimoto, Akihide; Tanaka, Maki; Yamano, Tomoki; Hsueh, Eddy; Hoon, Dave S B.

In: Clinical Cancer Research, Vol. 10, No. 7, 01.04.2004, p. 2351-2358.

Research output: Contribution to journalArticle

Takeuchi, H, Fujimoto, A, Tanaka, M, Yamano, T, Hsueh, E & Hoon, DSB 2004, 'CCL21 Chemokine Regulates Chemokine Receptor CCR7 Bearing Malignant Melanoma Cells', Clinical Cancer Research, vol. 10, no. 7, pp. 2351-2358. https://doi.org/10.1158/1078-0432.CCR-03-0195
Takeuchi, Hiroya ; Fujimoto, Akihide ; Tanaka, Maki ; Yamano, Tomoki ; Hsueh, Eddy ; Hoon, Dave S B. / CCL21 Chemokine Regulates Chemokine Receptor CCR7 Bearing Malignant Melanoma Cells. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 7. pp. 2351-2358.
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AU - Takeuchi, Hiroya

AU - Fujimoto, Akihide

AU - Tanaka, Maki

AU - Yamano, Tomoki

AU - Hsueh, Eddy

AU - Hoon, Dave S B

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N2 - Purpose: The chemokine CC-ligand 21/secondary lymphoid tissue chemokine (CCL21/SLC) regulates the homing of naïve T cells and dendritic cells that express CC-chemokine receptor 7 (CCR7) from distant sites to lymphoid tissue such as lymph nodes. We hypothesized that CCL21/SLC regulates the migration of CCR7-bearing melanoma cells from a primary lesion to regional tumor-draining lymph nodes. Experimental Design: Quantitative real-time reverse transcriptase-PCR (qRT) assay and immunohistochemistry (IHC) were used to assess the level of CCR7 expression in melanoma cell lines and in primary and metastatic melanoma tumors. Cell migration assay using melanoma cell lines was performed under the induction of CCL21/SLC. The CCL21/SLC expression level in tumor-draining sentinel lymph nodes (SLNs) was assessed by both qRT assay and IHC. Results: Melanoma cell lines and tumors demonstrated heterogeneous expression of CCR7 mRNA by qRT assay. There was strong functional correlation between CCR7 mRNA expression and cell migration induced by CCL21/SLC. IHC evidence of CCR7 expression in primary melanomas significantly (P = 0.02) correlated with Breslow thickness. Assessment of SLN from 55 melanoma patients by qRT assay demonstrated that CCL21/SLC mRNA expression level was significantly (P = 0.008) higher in pathologically melanoma-negative SLNs than in melanoma-positive SLNs. Conclusions: This report demonstrates a potential mechanism for recruitment and homing of CCR7(+) metastatic melanoma cells to tumor-draining lymph nodes, which express CCL21/SLC. The study also suggests that lymph nodes bearing metastasis may suppress CCL21/SLC production.

AB - Purpose: The chemokine CC-ligand 21/secondary lymphoid tissue chemokine (CCL21/SLC) regulates the homing of naïve T cells and dendritic cells that express CC-chemokine receptor 7 (CCR7) from distant sites to lymphoid tissue such as lymph nodes. We hypothesized that CCL21/SLC regulates the migration of CCR7-bearing melanoma cells from a primary lesion to regional tumor-draining lymph nodes. Experimental Design: Quantitative real-time reverse transcriptase-PCR (qRT) assay and immunohistochemistry (IHC) were used to assess the level of CCR7 expression in melanoma cell lines and in primary and metastatic melanoma tumors. Cell migration assay using melanoma cell lines was performed under the induction of CCL21/SLC. The CCL21/SLC expression level in tumor-draining sentinel lymph nodes (SLNs) was assessed by both qRT assay and IHC. Results: Melanoma cell lines and tumors demonstrated heterogeneous expression of CCR7 mRNA by qRT assay. There was strong functional correlation between CCR7 mRNA expression and cell migration induced by CCL21/SLC. IHC evidence of CCR7 expression in primary melanomas significantly (P = 0.02) correlated with Breslow thickness. Assessment of SLN from 55 melanoma patients by qRT assay demonstrated that CCL21/SLC mRNA expression level was significantly (P = 0.008) higher in pathologically melanoma-negative SLNs than in melanoma-positive SLNs. Conclusions: This report demonstrates a potential mechanism for recruitment and homing of CCR7(+) metastatic melanoma cells to tumor-draining lymph nodes, which express CCL21/SLC. The study also suggests that lymph nodes bearing metastasis may suppress CCL21/SLC production.

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