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Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells

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Abstract

Background: CXCR4, the chemokine receptor for CXCL12, has recently been involved in the metastatic process of several neoplasms. Materials and methods: The expression of CXCR4 was evaluated by immunohistochemistry of colorectal tissue samples and by flow cytometry on Caco2, GEO, SW480, SW48, Lovo and SW620 human colon carcinoma cell lines. Correlations with pathological characteristics of the specimens were analysed with chi-square test. To verify the functional status of CXCR4, cell lines were tested in adhesion, migration, and proliferation assays. Results: We studied the expression of CXCR4 in 88 human colorectal tissues and we found that CXCR4 was expressed in >10% of epithelial cells in 50% of normal mucosae (7/14), in 55% of polyps (29/53), in all of carcinomas (16/16) and hepatic metastasis (5/5). Notably, CXCR4 was significantly over-expressed in cancerous lesions (carcinomas and metastasis) compared to non-cancerous lesions (normal mucosa and polyps) (P=0.003) and in adenomatous polyps versus hyperplastic polyps (P=0.009). The diameter of a polyp was also significantly associated with CXCR4 expression (P=0.031). SW480, SW48 and SW620 cell lines showed the highest levels of CXCR4 (60–80% of positive cells). Adhesion, migration, and proliferation increased in response to the CXCL12 chemokine. These effects were abrogated by the addition of anti-CXCR4 antibodies. Further, CXCL12 activated ERK1/2 in SW480 cells. Conclusions: These data suggest that CXCR4 might play a role in colon cancer cell properties and that anti-CXCR4 antibodies could have therapeutic effects against colorectal cancer.

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Acknowledgements

We thank Dr Maria Vittoria Barone (NCI—Naples) for her help in chemotaxis and adhesion experiments. We also thank Antonio Barbato and Fernando Caccavello for their technical assistance in the laboratories of the Department of Surgical Pathology. This work was supported by grants from Novartis (Dr Nora Pigna and Dr Saverio Valerio) and AstraZeneca (Dr Nino Sala).

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Authors and Affiliations

  1. Molecular and Cellular Biology, “Federico II” University, via Pansini, 80131, Naples, Italy

    Antonella di Palma & Angela Maria Acquaviva

  2. Division of Clinical Immunology, National Cancer Institute, via M. Semmola, 80131, Naples, Italy

    Alessandro Ottaiano, Maria Napolitano, Giuseppe Castello, Paolo Antonio Ascierto & Stefania Scala

  3. Division of Medical Oncology B, National Cancer Institute, via M. Semmola, 80131, Naples, Italy

    Carmen Pisano, Sandro Pignata & Rosario Vincenzo Iaffaioli

  4. Department of Surgical Pathology, National Cancer Institute, via M. Semmola, 80131, Naples, Italy

    Fabiana Tatangelo & Gerardo Botti

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  1. Alessandro Ottaiano
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  2. Antonella di Palma
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  3. Maria Napolitano
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  8. Angela Maria Acquaviva
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  12. Stefania Scala
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Correspondence to Alessandro Ottaiano.

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Ottaiano, A., di Palma, A., Napolitano, M. et al. Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells. Cancer Immunol Immunother 54, 781–791 (2005). https://doi.org/10.1007/s00262-004-0636-3

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  • DOI: https://doi.org/10.1007/s00262-004-0636-3

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