MedicalResearch.com Interview with:
Prof. Dr. Véronique Orian-Rousseau
Karlsruher Institut für Technologie (KIT)
Institut für Toxikologie und Genetik (ITG)
Medical Research: What is the background for this study? What are the main findings?
Response: Our group is working on the role of cell adhesion molecules in development and in tumor progression and metastasis. One protein in focus is CD44, a molecule that controls proliferation, differentiation and survival of cells. We have shown that one member of this family, namely CD44v6 acts as a co-receptor for receptor tyrosine kinases (RTKs) such as MET and VEGFR-2. CD44v6 has a dual function. It controls both the activation and signaling from the RTKs. We have identified a sequence in CD44v6 that is crucial for its function as a co-receptor. From this sequence we made a peptide that inhibits MET and VEGFR2 activation and signaling.
The CD44v6 peptide was used in several independent mouse models of pancreatic cancer including the transgenic PDAC mouse model. It could inhibit the growth of the primary tumor, metastasis and in addition could eliminate already established metastases.
In addition, we could show that MET and CD44v6 expression correlates with poor prognosis and metastasis in a cohort of pancreatic cancer patients.
Medical Research: What should clinicians and patients take away from your report?
Response: The take home message is that CD44v6 should be considered as a target for cancer therapy and more specifically in pancreatic cancer. Blocking of CD44v6 signaling seems to be very efficient in inhibiting pancreatic tumor growth, metastasis and the establishment of metastases in distant organs. The peptide represents a promising tool to fight pancreatic cancer.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: We have certainly only touched on the relevance of CD44v6 in tumor progression and metastasis. A broader picture of the function of CD44v6 in tumor cells and even in the tumor micorenvironment is necessary.
Alexandra Matzke-Ogi, Katharina Jannasch, Marine Shatirishvili, Beatrix Fuchs, Sara Chiblak, Jennifer Morton, Bouchra Tawk, Thomas Lindner, Owen Sansom, Frauke Alves, Arne Warth, Christian Schwager, Walter Mier, Jörg Kleeff, Helmut Ponta, Amir Abdollahi, Véronique Orian-Rousseau.
Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by interference with CD44v6 Signaling.Gastroenterology, 2015; DOI: 10.1053/j.gastro.2015.10.020
Prof. Dr. Véronique Orian-Rousseau (2015). Pancreatic Cancer May Be Inhibited By Signaling Peptide