Mechanobiology of tumor invasion: engineering meets oncology

Abstract

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.

Figure 1. Gross assessment of invasive carcinoma of the breast

Cut section of an invasive ductal carcinoma of the breast from an excisional biopsy specimen shows an infiltrative, stellate-shaped mass with a white cut surface.

Figure 2. Microscopic assessment of invasive carcinoma of the breast

Invasive tubular carcinoma of the breast, characterized by well-formed tubules and desmoplastic stroma (hematoxylin-eosin, 200X).

Figure 3. Immunohistochemical staining to distinguish between invasive carcinoma and benign breast tissue

Immunohistochemical staining for p63 shows absence of myoepithelium in invasive carcinoma (right), and highlights the nuclei of myoepithelium in benign breast ducts (left) (200x).