gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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Zoledronic Acid has Direct anti-Proliferative and anti-Metastatic Effect on Pancreatic Carcinoma Cells and Acts an Antigen for γ2 γ/δ T cells

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  • corresponding author presenting/speaker Angela Märten - Universitätsklinikum, Heidelberg, Deutschland
  • Marie von Lilienfeld-Toal - Universitätsklinikum, Bonn
  • Markus Büchler - Universitätsklinikum, Heidelberg
  • Dirk Jäger - NCT, Heidelberg
  • Jan Schmidt - Universitätsklinikum, Heidelberg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO129

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk239.shtml

Published: March 20, 2006

© 2006 Märten et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Background: Beside their use as anti-resorptive drug, bisphosphonates are well known to stimulate γ/δT cells and to have direct effects on tumor growth.

Methods: We determined the direct cytotoxic effect of pamidronate and zoledronic acid, the induction of apoptosis and their anti-metastatic potentials. Next, we analyzed how bisphosphonates acts on γ/δT cells propagated with our recently published protocol. The susceptibility of pancreatic carcinoma cells pretreated with bisphosphonates against γ/δT cells was tested in cytotoxicity assays and the subgroup involved in killing was investigated

Results: Zoledronic acid but not pamidronate has a cytotoxic potential even at physiological dosage. Zoledronic acid does not only induce apoptosis by inhibiting the Ras-pathway but has also an anti-metastatic effect. Fresh prepared γ/δT cells consisting mainly out of Vδ2 cells showed increased cytotoxicity against bisphosphonate-treated pancreatic carcinoma cells. gd T cells could be expanded four-fold by use of anti-CD3 and IL-2. However, these γ/δT cells do not respond to bisphosphonates and kill mainly in a Vδ1 dependent manner.

Conclusion: Our results demonstrate that zoledronic acid has a direct apoptotic effect on pancreatic carcinoma cells and has anti-metastatic properties. Tumor cells treated with zoledronic acid are more susceptible against Vγ9Vδ2 T cells, the most abundant population of γ/δT cells in the peripheral blood. Treatment with zoledronic acid for patients with pancreatic carcinoma might be an option.