Académie royale de Médecine de Belgique


Résumé de Peter Friedl (Séance du 28 novembre 2009)


par P. FRIEDL (University of Nijmegen – Pays-Bas), invité. 

Molecular programs controlling metastatic cancer progression are diverse in different cancers as well as within the microenvironment of a single lesion. These include amoeboid, mesenchymal and collective invasion processes, followed by different mechanisms to seed and condition the metastatic site for secondary survival and growth. Cancer plasticity may further supported as side-effect of therapeutic interference, prompting cellular and molecular adaptation programs. Examples for unexpected adaptation programs suited to overcome molecular interference are the mesenchymal-amoeboid transition after interference with surface proteases or surface integrins, the amoeboid-mesenchymal transition after interference with Rho/ROCK pathways, and the collective–to-amoeboid transition leading to the dissociation of multicellular lesions followed by amoeboid single-cell dissemination. Thus, an understanding of cellular plasticity of invasion programs will be important to better target cancer progression.

Multiphoton microscopy (MPM) has become the method of choice for investigating cell structure and function in tissues and organs, including the invasion and progression of cancer lesions. Using a novel approach of infrared-excited (IR-)MPM at wavelengths above 1080 nm that enhances deep tissue microscopy in orthotopic fibrosarcoma xenografts, we here show deep collective invasion strands of several hundred connected cells. These multicellular units proliferate and simultaneously move with velocities of up to 200 µm per day along pre-existing blood vessels but not tumor-induced neovessels and proliferate (“invasive growth”). These perivascular tumor cell strands further maintain invasion and robust survival during otherwise regression-inducing experimental radiation therapy. Thus, intravital deep tumor imaging by IR-MPM identifies the tumor-vessel interface as preferred niche of invasive growth and radioresistance.