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Tissue-specific differential antitumour effect of molecular forms of fractalkine in a mouse model of metastatic colon cancer
  1. S Vitale1,
  2. B Cambien1,
  3. B F Karimdjee1,
  4. R Barthel1,
  5. P Staccini3,
  6. C Luci2,
  7. V Breittmayer1,
  8. F Anjuère2,
  9. A Schmid-Alliana1,
  10. H Schmid-Antomarchi1
  1. 1INSERM U638 Université de Nice-Sophia Antipolis, Nice, France
  2. 2INSERM U721 Université de Nice-Sophia Antipolis, Nice, France
  3. 3CHU Département STI Santé, UFR Médecine, Université de Nice-Sophia Antipolis, Nice, France
  1. Correspondence to:
    Annie Schmid-Alliana
    Ph.D. INSERM U638, Faculté de Médecine, 28 Avenue de Valombrose, 06107 Nice Cedex 02, France;schmid{at}unice.fr

Abstract

Background and aims: Fractalkine, a chemokine that presents as both a secreted and a membrane-anchored form, has been described as having tumour-suppressive activities in standard subcutaneous models. Here, we investigate the antitumour effect of fractalkine, in its three molecular forms, in two orthotopic models of metastatic colon cancer (liver and lung) and in the standard subcutaneous model.

Methods: We have developed models of skin tumours, liver and pulmonary metastasis and compared the extent of tumour development between C26 colon cancer cells expressing either the native, the soluble, the membrane-bound fractalkine or none.

Results: The native fractalkine exhibits the strongest antitumour effect, reducing the tumour size by 93% in the skin and by 99% in the orthotopic models (p<0.0001). Its overall effect results from a critical balance between the activity of the secreted and the membrane-bound forms, balance that is itself dependent on the target tissue. In the skin, both molecular variants reduce tumour development by 66% (p<0.01). In contrast, the liver and lung metastases are only significantly reduced by the soluble form (by 96%, p<0.002) whereas the membrane-bound variant exerts a barely significant effect in the liver (p = 0.049) and promotes tumour growth in the lungs. Moreover, we show a significant difference in the contribution of the infiltrating leukocytes to the tumour-suppressive activity of fractalkine between the standard and the orthotopic models.

Conclusions: Fractalkine expression by C26 tumour cells drastically reduces their metastatic potential in the two physiological target organs. Both molecular forms contribute to its antitumour potential but exhibit differential effects on tumour development depending on the target tissue.

  • FKN, fractalkine
  • FKN-tot, total fractalkine
  • FKN-mb, membrane-bound fractalkine
  • FKN-sol, soluble fractalkine
  • colon cancer
  • immunotherapy
  • metastasis
  • chemokine
  • animal model

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Footnotes

  • Published Online First 26 July 2006

  • Grant support: This work was supported in part by the Institut National de la Santé et de la Recherche Médicale and by the Association pour la Recherche sur le Cancer (Grant 3412). BC is the recipient of a post-doctoral fellowship from the Association pour la Recherche sur le Cancer.

  • Competing interest: none declared.

  • The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Gut editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence (http://GUT.bmjjournals.com/ifora/licence.pdf.)

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