Cancer invasion into musculature: Mechanics, molecules and implications

Tumor invasion along structural interphases of surrounding tumor-free tissue represents a key process during tumor progression. Much attention has been devoted to mechanisms of tumor cell migration within extracellular matrix (ECM)-rich connective tissue, however a comprehensive understanding of tumor invasion into tissue of higher structural complexity, such as muscle tissue, is lacking. Muscle invasion in cancer patients is often associated with destructive growth and worsened prognosis. Here, we review biochemical, geometrical and mechanical cues of smooth and skeletal muscle tissues and their relevance for guided invasion of cancer cells. As integrating concept, muscle-organizing ECM-rich surfaces of the epi-, peri- and endomysium provide cleft-like confined spaces along interfaces between dynamic muscle cells, which provide molecular and physical cues that guide migrating cancer cells, forming a possible contribution to cancer progression.