Int. J. Dev. Biol. 54: 887 - 896 (2010)

https://doi.org/10.1387/ijdb.092948ow

Vol 54, Issue 5

Modeling and quantification of cancer cell invasion through collagen type I matrices

Technical Article | Published: 28 August 2009

Olivier De Wever*^,1, An Hendrix², Astrid De Boeck¹, Wendy Westbroek⁴,Geert Braems³, Shahin Emami^5,6, Michèle Sabbah⁵, Christian Gespach^5,6 and Marc Bracke¹

¹Laboratory of Experimental Cancer Research, Department of Radiotherapy and Nuclear Medicine, ²Department of Medical Oncology, and ³Department of Gynaecology, Ghent University Hospital, Gent, Belgium, ⁴National Human Genome Research Institute, NIH, Bethesda, Maryland, USA, ⁵INSERM U 673, Molecular and Clinical Oncology of Human Solid Tumors, ⁶INSERM U938 and Université Pierre et Marie Curie-Paris, Faculté de Médecine, Paris, France

Abstract

Tumor invasion is the outcome of a complex interplay between cancer cells and the stromal environment. Considering the contribution of the stromal environment, we developed a membrane-free single-cell and spheroid based complementary model to study cancer invasion through native collagen type-I matrices. Cell morphology is preserved during the assays allowing real time monitoring of invasion-induced changes in cell structure and F-actin organization. Combining these models with computerized quantification permits the calculation of highly reproducible and operator-independent data. These assays are versatile in the use of fluorescent probes and have a flexible kinetic endpoint. Once the optimal experimental conditions are empirically determined, the collagen type-I invasion assays can be used for preclinical validation of small-molecule inhibitors targeting invasion. Initiation and monitoring of the single-cell and spheroid invasion model can be achieved in 8 h (over 3 days) and in 14 h (over 8 days) respectively.

Keywords

invasion, collagen, stroma, 3D matrices, ecosystem