Mechanics, malignancy, and metastasis: the force journey of a tumor cell.

TitleMechanics, malignancy, and metastasis: the force journey of a tumor cell.
Publication TypeJournal Article
Year of Publication2009
AuthorsKumar S, Weaver VM
JournalCancer Metastasis Rev
Date Published2009 Jun
KeywordsAnimals, Biophysics, Cell Transformation, Neoplastic, Epigenesis, Genetic, Extracellular Matrix, Focal Adhesion Protein-Tyrosine Kinases, Humans, Lasers, Microscopy, Atomic Force, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, rho-Associated Kinases, Stress, Mechanical

A cell undergoes many genetic and epigenetic changes as it transitions to malignancy. Malignant transformation is also accompanied by a progressive loss of tissue homeostasis and perturbations in tissue architecture that ultimately culminates in tumor cell invasion into the parenchyma and metastasis to distant organ sites. Increasingly, cancer biologists have begun to recognize that a critical component of this transformation journey involves marked alterations in the mechanical phenotype of the cell and its surrounding microenvironment. These mechanical differences include modifications in cell and tissue structure, adaptive force-induced changes in the environment, altered processing of micromechanical cues encoded in the extracellular matrix (ECM), and cell-directed remodeling of the extracellular stroma. Here, we review critical steps in this "force journey," including mechanical contributions to tissue dysplasia, invasion of the ECM, and metastasis. We discuss the biophysical basis of this force journey and present recent advances in the measurement of cellular mechanical properties in vitro and in vivo. We end by describing examples of molecular mechanisms through which tumor cells sense, process and respond to mechanical forces in their environment. While our understanding of the mechanical components of tumor growth, survival and motility remains in its infancy, considerable work has already yielded valuable insight into the molecular basis of force-dependent tumor pathophysiology, which offers new directions in cancer chemotherapeutics.

Alternate JournalCancer Metastasis Rev.
PubMed ID19153673
PubMed Central IDPMC2658728
Grant List1DP2OD004213 / OD / NIH HHS / United States
7R01CA078731-07 / CA / NCI NIH HHS / United States
R01 CA078731-07 / CA / NCI NIH HHS / United States