Caveolin-1-negative head and neck squamous cell carcinoma primary tumors display increased epithelial to mesenchymal transition and prometastatic properties

Abstract

// Alain C. Jung 2 , Anne-Marie Ray 1 , Ludivine Ramolu 2 , Christine Macabre 2 , Florian Simon 1 , Fanny Noulet 1 , Anne-Florence Blandin 1 , Guillaume Renner 1 , Maxime Lehmann 1 , Laurence Choulier 1 , Horst Kessler 3 , Joseph Abecassis 2 , Monique Dontenwill 1 and Sophie Martin 1 1 Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France 2 Laboratoire de Biologie Tumorale, EA 3430 Université de Strasbourg, CRLC Paul Strauss, Strasbourg, France 3 Institute for Advanced Study and Center of Integrated Protein Studies, Technische Universität München, Department Chemie, Garching, Germany Correspondence to: Sophie Martin, email: // Keywords : caveolin-1, integrins, head and neck cancer, metastasis Received : May 18, 2015 Accepted : September 17, 2015 Published : October 12, 2015 Abstract Distant metastases arise in 20-30% of patients with squamous cell carcinoma of the head and neck (HNSCC) in the 2 years following treatment. Therapeutic options are limited and the outcome of the patients is poor. The identification of predictive biomarkers of patient at risk for distant metastasis and therapies are urgently needed. We previously identified a clinical subgroup, called “R1” characterized by high propensity for rapid distant metastasis. Here, we showed that “R1” patients do not or at very low level express caveolin-1 (Cav1). Low or no expression of Cav1 is of bad prognosis. Disappearance of Cav1 enables cells to undergo epithelial-mesenchymal transition (EMT). EMT is associated with enhanced migration and invasion. Our study uncovered a new target, α 5 β 1 integrin. Targeting α 5 β 1 integrins might not only prevent metastasis of HNSCC but also delay the development of the primary tumor by reducing tumor cell viability. Cav1 detection might be taken into consideration in the future in the clinic not only to identify patients at high risk of metastasis but also to select patient who might benefit from an anti-integrin therapy.