The Physical Factors Involved in Cancer Progression

Mechanical forces, generated externally and internally, regulate cancer development. Cancer continues to be a disease that is difficult to be healed despite medical and scientific advancement. Advances in knowledge of the mechanical properties have led to new insights in cancer mechanobiology. This review is focused on four main directions: the physical forces found in the in vivo microenvironment, function of cellular and of tissue stiffness in cancer progression, and beneficial effects of physical exercise on cancer suppression. Physical forces in vivo include stretching, compression, shear stress, tension, contraction and relaxation. Due to the loss of contractile units such as tropomyosin 2.1 (Tpm 2.1), cancer cells are unable to transduce the physical force from the extracellular matrix (ECM), through ECM receptors such as β1 integrin, to cytoskeletal proteins like actomyosin. This results in reduced stiffness and loss of rigidity sensing ability in cancer cells, leading to uncontrolled cell proliferation. In order to reestablish homeostasis, cancer cells continue to grow, secrete growth factors, cytokines, and deposit ECM. Cancer-associated fibroblasts (CAFs) assist in ECM secretion and remodeling. On the one hand, the cancer tissue is being remodeled to a tumor, on the other hand, the remodeled tumor tissue also enhances the invasiveness of cancer cells. In summary, tumor development may be viewed as a process that reflects the mechanism employed in wound healing. This review emphasizes the role of physical forces that help shape tumor growth.