Jain, R. K., Martin, J. D. & Stylianopoulos, T. The role of mechanical forces in tumor growth and therapy. Annu. Rev. Biomed. Eng. 16, 321–346 (2014).
Chaudhuri, O. et al. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat. Mater. 13, 970–978 (2014).
Mouw, J. K. et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat. Med. 20, 360–367 (2014).
Samuel, M. S. et al. Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell 19, 776–791 (2011).
Wirtz, D., Konstantopoulos, K. & Searson, P. C. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11, 512–522 (2011).
Goetz, J. G. et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 146, 148–163 (2011).
Tung, J. C. et al. Tumor mechanics and metabolic dysfunction. Free Radic. Biol. Med. 79, 269–280 (2015).
Helmlinger, G., Netti, P. A., Lichtenbeld, H. C., Melder, R. J. & Jain, R. K. Solid stress inhibits the growth of multicellular tumor spheroids. Nat. Biotechnol. 15, 778–783 (1997).
Stylianopoulos, T. et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc. Natl Acad. Sci. USA 109, 15101–15108 (2012).
Boucher, Y. & Jain, R. K. Microvascular pressure is the principal driving force for interstitial hypertension in solid tumors: implications for vascular collapse. Cancer Res. 52, 5110–5114 (1992).
Griffon-Etienne, G., Boucher, Y., Brekken, C., Suit, H. D. & Jain, R. K. Taxane-induced apoptosis decompresses blood vessels and lowers interstitial fluid pressure in solid tumors: clinical implications. Cancer Res. 59, 3776–3782 (1999).
Padera, T. P. et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 296, 1883–1886 (2002).
Padera, T. P. et al. Pathology: cancer cells compress intratumour vessels. Nature 427, 695 (2004).
Chauhan, V. P. et al.
Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat. Commun. 4, 2516 (2013).
Jain, R. K. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell 26, 605–622 (2014).
Fernández-Sánchez, M. E. et al. Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure. Nature 523, 92–95 (2015).
Tse, J. M. et al. Mechanical compression drives cancer cells toward invasive phenotype. Proc. Natl Acad. Sci. USA 109, 911–916 (2012).
Provenzano, P. P. et al. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21, 418–429 (2012).
Chauhan, V. P. et al. Compression of pancreatic tumor blood vessels by hyaluronan is caused by solid stress and not interstitial fluid pressure. Cancer Cell 26, 14–15 (2014).
US National Library of Medicine. Proton w/FOLFIRINOX-Losartan for pancreatic cancer. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01821729 (2013).
US National Library of Medicine. PEGPH20 plus nab-paclitaxel plus Gemcitabine compared with nab-paclitaxel plus Gemcitabine in subjects with stage IV untreated pancreatic cancer (HALO-109-202). ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01839487 (2013).
Chuong, C. & Fung, Y. in Frontiers in Biomechanics (eds Schmid-Schönbein, G. W. et al.
) Ch. 9 (Springer, 1986).
Taber, L. A. & Humphrey, J. D. Stress-modulated growth, residual stress, and vascular heterogeneity. J. Biomech. Eng. 123, 528–535 (2001).
Campas, O. et al. Quantifying cell-generated mechanical forces within living embryonic tissues. Nat. Methods 11, 183–189 (2014).
Grashoff, C. et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263–266 (2010).
Timoshenko, S. & Goodier, J. N. Theory of Elasticity (McGraw-Hill, 1951).
Plodinec, M. et al. The nanomechanical signature of breast cancer. Nat. Nanotech. 7, 757–765 (2012).
Lopez, J., Kang, I., You, W., McDonald, D. & Weaver, V.
In situ force mapping of mammary gland transformation. Integr. Biol. (Camb). 3, 910–921 (2011).
Vakoc, B. J. et al. Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat. Med. 15, 1219–1223 (2009).
Simon, D., Horgan, C. & Humphrey, J. Mechanical restrictions on biological responses by adherent cells within collagen gels. J. Mech. Behav. Biomed. Mat. 14, 216–226 (2012).
Orimo, A. et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121, 335–348 (2005).
Stylianopoulos, T. et al. Coevolution of solid stress and interstitial fluid pressure in tumors during progression: implications for vascular collapse. Cancer Res. 73, 3833–3841 (2013).
Voutouri, C., Mpekris, F., Papageorgis, P., Odysseos, A. D. & Stylianopoulos, T. Role of constitutive behavior and tumor-host mechanical interactions in the state of stress and growth of solid tumors. PLoS ONE 9, e104717 (2014).
Fukumura, D., Incio, J., Shankaraiah, R. & Jain, R. K. Obesity and cancer: an angiogenic and inflammatory link. Microcirculation 23, 191–206 (2016).
Incio, J. et al. Obesity-induced inflammation and desmoplasia promote pancreatic cancer progression and resistance to chemotherapy. Cancer Discov. 6, 852–869 (2016).
Van den Eynden, G. G. et al. The histological growth pattern of colorectal cancer liver metastases has prognostic value. Clin. Exp. Metastasis 29, 541–549 (2012).
Eefsen, R. et al. Growth pattern of colorectal liver metastasis as a marker of recurrence risk. Clin. Exp. Metastasis 32, 369–381 (2015).
Conklin, M. W. et al. Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am. J. Pathol. 178, 1221–1232 (2011).
Good, D. W. et al. Elasticity as a biomarker for prostate cancer: a systematic review. BJU. Int. 113, 523–534 (2014).
Choi, W. J. et al. Predicting prognostic factors of breast cancer using shear wave elastography. Ultrasound Med. Biol. 40, 269–274 (2014).
Milosevic, M. F. et al. High tumor interstitial fluid pressure identifies cervical cancer patients with improved survival from radiotherapy plus cisplatin versus radiotherapy alone. Int. J. Cancer 135, 1692–1699 (2014).
Roh, H. et al. Interstitial hypertension in carcinoma of uterine cervix in patients: possible correlation with tumor oxygenation and radiation response. Cancer Res. 51, 6695–6698 (1991).
Fyles, A. et al. Long-term performance of interstial fluid pressure and hypoxia as prognostic factors in cervix cancer. Radiother. Oncol. 80, 132–137 (2006).
Discher, D. E., Janmey, P. & Wang, Y. L. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005).
Nia, H. T., Han, L., Li, Y., Ortiz, C. & Grodzinsky, A. Poroelasticity of cartilage at the nanoscale. Biophys. J. 101, 2304–2313 (2011).
Grodzinsky, A. J. Fields, Forces, and Flows in Biological Systems Ch. 4 (Garland Science, 2011).
Hutter, J. L. & Bechhoefer, J. Calibration of atomic-force microscope tips. Rev. Sci. Instrum. 64, 1868–1873 (1993).
Kiviranta, P. et al. Collagen network primarily controls Poisson's ratio of bovine articular cartilage in compression. J. Orthop. Res. 24, 690–699 (2006).
Buschmann, M. D. et al. Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow. Arch. Biochem. Biophys. 366, 1–7 (1999).
Netti, P. A., Berk, D. A., Swartz, M. A., Grodzinsky, A. J. & Jain, R. K. Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res. 60, 2497–2503 (2000).
Morimoto-Tomita, M., Ohashi, Y., Matsubara, A., Tsuiji, M. & Irimura, T. Mouse colon carcinoma cells established for high incidence of experimental hepatic metastasis exhibit accelerated and anchorage-independent growth. Clin. Exp. Metastasis 22, 513–521 (2005).
Yuan, F. et al. Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. Cancer Res. 54, 4564–4568 (1994).
Nia, H. T. et al. Dataset for solid stress and elastic energy as measures of tumour mechanopathology. figshare http://dx.doi.org/10.6084/m9.figshare.3796092 (2016).