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Open Access Highly Accessed Research article

Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

Sandra Pinto12, Alicia Martínez-Romero1, José-Enrique O’Connor1, Rosario Gil-Benso3, Teresa San-Miguel3, Liria Terrádez3, Carlos Monteagudo34 and Robert C Callaghan13*

Author Affiliations

1 Cytomics Laboratory, Mixed Unit CIPF-UVEG, Príncipe Felipe Research Centre, Valencia, Avda Autopista del Saler, 16, 46012 Valencia, Spain

2 Current address: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra Portugal

3 Department of Pathology, University of Valencia, Avda. Blasco Ibañez 15, 46010 Valencia Spain

4 Department of Pathology, University Clinic Hospital INCLIVA, Avda. Blasco Ibañez 17, 46010 Valencia, Spain

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BMC Cancer 2014, 14:118  doi:10.1186/1471-2407-14-118

Published: 22 February 2014

Abstract

Background

Chemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival.

Methods

In this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and cell lines derived from them were also analyzed.

Results

Our results show that the melanoma cell lines do not express or express in a low degree the chemokine receptors on their cell surface. However, melanoma cell lines show intracellular expression of all the aforementioned receptors and most of their respective ligands. When analyzing the xenografts and the cell lines obtained from them we found variations in the intracellular expression of chemokines and chemokine receptors that differed between the primary and metastatic cell lines. However, as well as in the original cell lines, minute or no expression of the chemokine receptors was observed at the cell surface.

Conclusions

Coexpression of chemokine receptors and their ligands was found in human melanoma cell lines. However, this expression is intracellular and receptors are not found at the cell membrane nor chemokines are secreted to the cell medium. The levels of expressed chemokine receptors and their ligands show dynamic variations after xenotransplantation that differ depending on the origin of the cell line (from primary tumor or from metastasis).

Keywords:
Melanoma; Cell line; Chemokine receptor; Chemokine; Xenotransplantation