Journal
SEMINARS IN CANCER BIOLOGY
Volume 22, Issue 5-6, Pages 385-395Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2012.05.002
Keywords
Tumor; Stroma; Metastasis; Invasion; Biomechanical forces; Collagen
Categories
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of National Institutes of Health (NIH) [AR46574, AR45748, AR059203, AR051636]
- Weill Cornell Medical College's National Center for Research Resources (NIH) Clinical and Translational Science Center [TL1RR024998, UL1RR024996]
- Weill Cornell Graduate School of Medical Sciences
- Swedish Research Council
- Georg and Eva Klein Visiting Junior Scientist Award
- Sigurd och Elsa Goljes minne
- American Scandinavia Foundation
- VINNMER-Marie Curie international
- National Center for Research Resources, National Institutes of Health [C06-RR12538-01]
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Tumor metastases and epithelial to mesenchymal transition (EMT) involve tumor cell invasion and migration through the dense collagen-rich extracellular matrix surrounding the tumor. Little is neither known about the mechanobiological mechanisms involved in this process, nor the role of the mechanical forces generated by the cells in their effort to invade and migrate through the stroma. In this paper we propose a new fundamental mechanobiological mechanism involved in cancer growth and metastasis, which can be both protective or destructive depending on the magnitude of the forces generated by the cells. This new mechanobiological mechanism directly challenges current paradigms that are focused mainly on biological and biochemical mechanisms associated with tumor metastasis. Our new mechanobiological mechanism describes how tumor expansion generates mechanical forces within the stroma to not only resist tumor expansion but also inhibit or enhance tumor invasion by, respectively, inhibiting or enhancing matrix metalloproteinase (MMP) degradation of the tensed interstitial collagen. While this mechanobiological mechanism has not been previously applied to the study of tumor metastasis and EMT, it may have the potential to broaden our understanding of the tumor invasive process and assist in developing new strategies for preventing or treating cancer metastasis. (C) 2012 Elsevier Ltd. All rights reserved.
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