Morphological quantification of proliferation to invasion transition in tumor spheroids

Abstract

Metastasis determines the lethality of cancer. In most clinical cases, patients are able to live with tumor proliferation before metastasis. Thus, the transition from tumor proliferation to metastasis/invasion is essential.However, the mechanism is still unclear andespecially, the proliferation to metastasis/invasion transition point has not been well defined. Therefore,quantitative characterization of this transition is urgently needed.Methods: We have successfully developed a home built living cell incubation system combined with an inverted optical microscope, and a systematic, quantitative approach to describing the major characteristic morphological parameters for the identification of the critical transition points for tumor cell spheroids in a collagen fiber scaffold. Results: The system focuses on in vitro tumor modeling, e.g. the development of tumor cell spheroids in a collagen fiber scaffold and the monitoring of cell transition from proliferation to invasion. By applying this approach to multiple tumor spheroid models, such as U87 (glioma tumor), H1299 (lung cancer), and MDAMB231 (breast cancer) cells, we have obtained quantitative morphological references to evaluate the proliferation to invasion transition time, as well as differentiating the invasion potential of tumor cells upon environmental changes, i.e. drug