Mechanobiology of tumor invasion: Engineering meets oncology

The physical sciences and engineering have introduced novel perspectives into the study of cancer through model systems, tools, and metrics that enable integration of basic science observations with clinical data. These methods have contributed to the identification of several overarching mechanisms that drive processes during cancer progression including tumor growth, angiogenesis, and metastasis. During tumor cell invasion – the first clinically observable step of metastasis – cells demonstrate diverse and evolving physical phenotypes that cannot typically be defined by any single molecular mechanism, and mechanobiology has been used to study the physical cell behaviors that comprise the “invasive phenotype”. In this review, we discuss the continually evolving pathological characterization and in vitro mechanobiological characterization of tumor invasion, with emphasis on emerging physical biology and mechanobiology strategies that have contributed to a more robust mechanistic understanding of tumor cell invasion. These physical approaches may ultimately help to better predict and identify tumor metastasis.

► Tumor invasion, the process by which cells physically dissociate from primary tumors, is a rate-limiting step in metastasis.
► Invasion depends on coordination of intracellular molecular machinery and response to biophysical extracellular cues.
► Mechanobiology and engineering have been used to study physical tumor cell behaviors that comprise the “invasive phenotype”.
► Understanding the invasive phenotype should enable more effective diagnostic and therapeutic strategies in the clinic.