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Research Paper
Development of a Conditional Bioluminescent Transplant Model for TPM3-ALK-Induced Tumorigenesis as a Tool to Validate ALK-Dependent Cancer Targeted Therapy
Sylvie Giuriato, Nathalie Faumont, Emilie Bousquet, Marianne Foisseau, Anne Bibonne, Marc Moreau, Talal Al Saati, Dean W. Felsher, Georges Delsol and Fabienne Meggetto
volume 6 | issue 8
August 2007Pages: 1318 - 1323
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Overexpression and activation of TPM3-ALK tyrosine kinase fusion protein is a causal oncogenic event in the development of Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic ALK-positive tumours. Thus, the development of ALK specific tyrosine kinase inhibitors is a current therapeutic challenge. Animal models are essential to assess, in vivo, the efficiency of ALK-oncogene inhibitors and to identify new and/or additional therapeutic targets in the ALK tumorigenesis pathway. Using the tetracycline system to allow conditional and concomitant TPM3-ALK and luciferase expression, we have developed a unique transplant model for bioluminescent TPM3-ALK-induced fibroblastic tumours in athymic nude mice. The reversible TPM3-ALK expression allowed us to demonstrate that this oncogene is essential for the tumour growth and its maintenance. In addition, we showed that this model could be used to precisely assess tumour growth inhibition upon ALK chemical inactivation. As proof of principle, we used the general tyrosine kinase inhibitor herbimycin A to inhibit ALK oncoprotein activity. As expected, herbimycin A treatment reduced tumour growth as assessed both by tumour volume measurement and bioluminescent imaging. We conclude that this transplant model for TPM3-ALK-induced tumours represents a valuable tool not only to accurately and rapidly evaluate in vivo ALK-targeted therapies but also to gain insight into the mechanism of ALK-positive tumour development.
Authors
Sylvie Giuriato
Université Toulouse III Paul Sabatier, Toulouse, France
Nathalie Faumont
Université Toulouse III Paul Sabatier, Toulouse, France
Emilie Bousquet
Université Toulouse III Paul Sabatier, Toulouse, France
Marianne Foisseau
Université Toulouse III Paul Sabatier, Toulouse, France
Anne Bibonne
Université Paul Sabatier, Toulouse, France
Marc Moreau
Université Paul Sabatier, Toulouse, France
Talal Al Saati
Plateau technique d'Histopathologie Expérimentale de l'IFR30; Toulouse, France
Dean W. Felsher
Stanford University, Stanford, California USA
Georges Delsol
Universit 0054oulouse III Paul Sabatier; Toulouse, France
Fabienne Meggetto
Université Toulouse III Paul Sabatier,Toulouse, France
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.