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CXCR5 may be involved in the attraction of human metastatic neuroblastoma cells to the bone marrow

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Abstract

Introduction

Up-regulation of some chemokine receptors on tumor cells is associated with increased metastatic potential. In this respect, limited information is available on chemokine receptor in human neuroblastoma (NB).

Objects

Purpose of the study was to identify chemokines/chemokine receptors involved in bone marrow (BM) localization of metastatic NB cells in view of the development of targeted therapeutic strategies. CD45− metastatic NB cells were isolated from the BM of six patients by immunomagnetic bead manipulation. Some experiments were carried out using a panel of human neuroblastoma cell lines (GI-ME-N, GI-LI-N, LAN-5, HTLA-230, SH-SY-5Y and IMR-32). Immunophenotypic analyses were performed by flow cytometry. Cell migration assays were carried out using transwell systems. Calcium ion mobilization, chemokine receptor internalization and cell proliferation were investigated by flow cytometry.

Results

In all BM samples, CXCR5 was expressed by the majority of primary neuroblasts and mediated their chemotaxis in response to CXCL13. Primary metastatic NB cells from all BM samples expressed CXCR6, but were not attracted by soluble CXCL16. Studies performed with two CXCR6+ NB cell lines showed that the mechanism whereby neuroblasts did not migrate to CXCL16 was likely related to defective calcium ion mobilization.

Conclusions

CXCR5 is the first chemokine receptor so far identified able to attract in vitro primary metastatic NB cells. CXCR6 may be involved in retention of metastatic neuroblasts in the BM through interaction with CXCL16 expressing stromal cells in the absence of signal transduction.

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Acknowledgments

We are grateful to Dr. Maria Valeria Corrias and Barbara Carlini for providing patient BM samples and to Mrs. Chiara Bernardini for the excellent secretarial assistance. This study has been supported by grants from Compagnia San Paolo, Italy, to VP. IA is supported by Fondazione Gaslini, Genova, Italy and AIRC, Milano, Italy. CC and FM are the recipient of a fellowship from FIRC, Milano, Italy.

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Authors and Affiliations

  1. Department of Experimental and Laboratory Medicine, G. Gaslini Institute, Largo G. Gaslini 5, 16147, Genova, Italy

    Irma Airoldi

  2. Laboratory of Oncology, G. Gaslini Institute, Largo G. Gaslini 5, 16147, Genova, Italy

    Irma Airoldi, Claudia Cocco, Fabio Morandi, Ignazia Prigione & Vito Pistoia

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  1. Irma Airoldi
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  2. Claudia Cocco
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  3. Fabio Morandi
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  4. Ignazia Prigione
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  5. Vito Pistoia
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Correspondence to Irma Airoldi.

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Airoldi, I., Cocco, C., Morandi, F. et al. CXCR5 may be involved in the attraction of human metastatic neuroblastoma cells to the bone marrow. Cancer Immunol Immunother 57, 541–548 (2008). https://doi.org/10.1007/s00262-007-0392-2

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  • DOI: https://doi.org/10.1007/s00262-007-0392-2

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