The mechanical microenvironment in cancer: How physics affects tumours.
The tumour microenvironment contributes greatly to the response of tumour cells. It consists of chemical gradients, for example of oxygen and nutrients. However, a physical environment is also present. Apart from chemical input, cells also receive physical signals. Tumours display unique mechanical properties: they are a lot stiffer than normal tissue. This may be either a cause or a consequence of cancer, but literature suggests it has a major impact on tumour cells as will be described in this review. The mechanical microenvironment may cause malignant transformation, possibly through activation of oncogenic pathways and inhibition of tumour suppressor genes. In addition, the mechanical microenvironment may promote tumour progression by influencing processes such as epithelial-to-mesenchymal transition, enhancing cell survival through autophagy, but also affects sensitivity of tumour cells to therapeutics. Furthermore, multiple intracellular signalling pathways prove sensitive to the mechanical properties of the microenvironment. It appears the increased stiffness is unlikely to be caused by increased stiffness of the tumour cells themselves. However, there are indications that tumours display a higher cell density, making them more rigid. In addition, increased matrix deposition in the tumour, as well as increased interstitial fluid pressure may account for the increased stiffness of tumours. Overall, tumour mechanics are significantly different from normal tissue. Therefore, this feature should be further explored for use in cancer prevention, detection and treatment.
Radboud University, Institute for Molecules and Materials, Department of Molecular Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. Electronic address: a.nagelkerke@science.ru.nl.
Anika
A
Nagelkerke
Department of Radiation Oncology, Radboud University Medical Center, Geert grooteplein-zuid 32, 6525 GA Nijmegen, The Netherlands. Electronic address: jan.bussink@radboudumc.nl.
Johan
J
Bussink
Radboud University, Institute for Molecules and Materials, Department of Molecular Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. Electronic address: a.rowan@science.ru.nl.
Alan E
AE
Rowan
Department of Radiation Oncology, Radboud University Medical Center, Geert grooteplein-zuid 32, 6525 GA Nijmegen, The Netherlands. Electronic address: paul.span@radboudumc.nl.
Paul N
PN
Span
D000818:Animals; D002450:Cell Communication; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D055595:Mechanical Phenomena; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015398:Signal Transduction; D016896:Treatment Outcome; D059016:Tumor Microenvironment
Cancer; Intracellular signalling; Mechanics; Microenvironment; Therapeutic sensitivity