Intravital imaging reveals p53-dependent cancer cell death induced by phototherapy via calcium signaling
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Carlotta Giorgi1,*, Massimo Bonora1,*, Sonia Missiroli1, Federica Poletti1, Fabian Galindo Ramirez2,3, Giampaolo Morciano1, Claudia Morganti1, Pier Paolo Pandolfi4, Fabio Mammano2 and Paolo Pinton1
1 Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA center, University of Ferrara, Ferrara, Italy
2 Department of Physics and Astronomy, University of Padua, and Venetian Institute of Molecular Medicine, Padua, Italy
3 Instituto de fisiologia, Benemerita Universidad Autónoma de Puebla (BUAP), Puebla, Mexico
4 Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
* These authors contributed equally to this work
Paolo Pinton, email:
Keywords: Calcium (Ca2+), cell death, apoptosis, TRP53 (p53), mitochondria
Received: July 20, 2014 Accepted: December 01, 2014 Published: December 02, 2014
One challenge in biology is signal transduction monitoring in a physiological context. Intravital imaging techniques are revolutionizing our understanding of tumor and host cell behaviors in the tumor environment. However, these deep tissue imaging techniques have not yet been adopted to investigate the second messenger calcium (Ca2+). In the present study, we established conditions that allow the in vivo detection of Ca2+ signaling in three-dimensional tumor masses in mouse models. By combining intravital imaging and a skinfold chamber technique, we determined the ability of photodynamic cancer therapy to induce an increase in intracellular Ca2+ concentrations and, consequently, an increase in cell death in a p53-dependent pathway.
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