Mechanotransduction in cancer.

Tissue stiffness is tightly controlled under normal conditions, but changes with disease. In cancer, tumors often tend to be stiffer than the surrounding uninvolved tissue, yet the cells themselves soften. Within the past decade, and particularly in the last few years, there is increasing evidence that the stiffness of the extracellular matrix modulates cancer and stromal cell mechanics and function, influencing such disease hallmarks as angiogenesis, migration, and metastasis. This review briefly summarizes recent studies that investigate how cancer cells and fibrosis-relevant stromal cells respond to ECM stiffness, the possible sensing appendages and signaling mechanisms involved, and the emergence of novel substrates - including substrates with scar-like fractal heterogeneity - that mimic the in vivo mechanical environment of the cancer cell.

[1]  B. Ebert,et al.  Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. , 2015, Cell stem cell.

[2]  T. Saif,et al.  A mechanically-induced colon cancer cell population shows increased metastatic potential , 2014, Molecular Cancer.

[3]  P. Janmey,et al.  Augmentation of integrin-mediated mechanotransduction by hyaluronic acid. , 2014, Biomaterials.

[4]  Mikala Egeblad,et al.  Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling , 2009, Cell.

[5]  Michael W Davidson,et al.  Force engages vinculin and promotes tumor progression by enhancing PI3K activation of phosphatidylinositol (3,4,5)-triphosphate. , 2014, Cancer research.

[6]  M. Dembo,et al.  Substrate flexibility regulates growth and apoptosis of normal but not transformed cells. , 2000, American journal of physiology. Cell physiology.

[7]  Harry Heinzelmann,et al.  Increased plasticity of the stiffness of melanoma cells correlates with their acquisition of metastatic properties. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[8]  Jianbo Wang,et al.  Alterations in mechanical properties are associated with prostate cancer progression , 2014, Medical Oncology.

[9]  Yong Li,et al.  Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression , 2014, Nature Communications.

[10]  Lap Man Lee,et al.  A microfluidic pipette array for mechanophenotyping of cancer cells and mechanical gating of mechanosensitive channels. , 2015, Lab on a chip.

[11]  Jing Guo,et al.  High-Resolution Mechanical Imaging of Glioblastoma by Multifrequency Magnetic Resonance Elastography , 2014, PloS one.

[12]  A. J. Putnam,et al.  Endothelial cell traction and ECM density influence both capillary morphogenesis and maintenance in 3-D. , 2009, American journal of physiology. Cell physiology.

[13]  Adam J. Engler,et al.  Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance , 2006 .

[14]  V. Kosma,et al.  Prognostic value of hyaluronan expression in non‐small‐cell lung cancer: Increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma , 2001, International journal of cancer.

[15]  Thomas E Yankeelov,et al.  Assessing the accuracy and reproducibility of modality independent elastography in a murine model of breast cancer , 2015, Journal of medical imaging.

[16]  Catherine C. Park,et al.  Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. , 2015, Integrative biology : quantitative biosciences from nano to macro.

[17]  D. Radisky,et al.  Matrix compliance regulates Rac1b localization, NADPH oxidase assembly, and epithelial–mesenchymal transition , 2012, Molecular biology of the cell.

[18]  H. Tian,et al.  Yes-associated protein regulates the growth of human non-small cell lung cancer in response to matrix stiffness. , 2015, Molecular medicine reports.

[19]  M. Soloway,et al.  Evaluation of the prognostic potential of hyaluronic acid and hyaluronidase (HYAL1) for prostate cancer. , 2003, Cancer research.

[20]  E. Jabbari,et al.  Optimum 3D Matrix Stiffness for Maintenance of Cancer Stem Cells Is Dependent on Tissue Origin of Cancer Cells , 2015, PloS one.

[21]  Shawn P. Carey,et al.  Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks. , 2015, American journal of physiology. Cell physiology.

[22]  Lucas R. Smith,et al.  Collagen content does not alter the passive mechanical properties of fibrotic skeletal muscle in mdx mice. , 2014, American journal of physiology. Cell physiology.

[23]  B. Hinz,et al.  Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix , 2007, The Journal of cell biology.

[24]  Kevin W. Eliceiri,et al.  The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis , 2013, Nature Cell Biology.

[25]  Albert C. Chen,et al.  Title Matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a TWIST 1G 3 BP 2 mechanotransduction pathway , 2015 .

[26]  Florian Rehfeldt,et al.  Hyaluronic acid matrices show matrix stiffness in 2D and 3D dictates cytoskeletal order and myosin-II phosphorylation within stem cells. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[27]  M. Falk,et al.  Primary cilia found on HeLa and other cancer cells , 2015, Cell biology international.

[28]  B. Toole,et al.  Hyaluronan: from extracellular glue to pericellular cue , 2004, Nature Reviews Cancer.

[29]  F. Vizoso,et al.  Expression and prognostic significance of fibronectin and matrix metalloproteases in breast cancer metastasis , 2014, Histopathology.

[30]  B. Asselain,et al.  Serum hyaluronan (hyaluronic acid) in breast cancer patients , 1990, International journal of cancer.

[31]  G. Davis,et al.  Hepatocellular Carcinoma: Management of an Increasingly Common Problem , 2008, Proceedings.

[32]  D. Gourdon,et al.  Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells , 2015, Biomaterials.

[33]  Urszula Zaleska-Dorobisz,et al.  Ultrasound elastography - review of techniques and its clinical applications. , 2014, Advances in clinical and experimental medicine : official organ Wroclaw Medical University.

[34]  Takeo Matsumoto,et al.  Mechanical trapping of the nucleus on micropillared surfaces inhibits the proliferation of vascular smooth muscle cells but not cervical cancer HeLa cells. , 2015, Journal of biomechanics.

[35]  Amit Pathak,et al.  Topographic confinement of epithelial clusters induces epithelial-to-mesenchymal transition in compliant matrices , 2016, Scientific Reports.

[36]  Prashanth Asuri,et al.  Three‐dimensional matrix stiffness and adhesive ligands affect cancer cell response to toxins , 2016, Biotechnology and bioengineering.

[37]  Hui Zhang,et al.  Increased beta1 integrin is associated with decreased survival in invasive breast cancer. , 2007, Cancer research.

[38]  K. Stroka,et al.  Physical biology in cancer. 4. Physical cues guide tumor cell adhesion and migration. , 2014, American journal of physiology. Cell physiology.

[39]  V. Kosma,et al.  High stromal hyaluronan level is associated with poor differentiation and metastasis in prostate cancer. , 2001, European journal of cancer.

[40]  C. Mann,et al.  Aberrant repair and fibrosis development in skeletal muscle , 2011, Skeletal Muscle.

[41]  V. Lokeshwar,et al.  Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors , 2003, International journal of cancer.

[42]  Cynthia A. Reinhart-King,et al.  Tissue stiffness regulates serine/arginine-rich protein-mediated splicing of the extra domain B-fibronectin isoform in tumors , 2015, Proceedings of the National Academy of Sciences.

[43]  Z. Ren,et al.  Increasing matrix stiffness upregulates vascular endothelial growth factor expression in hepatocellular carcinoma cells mediated by integrin β1. , 2014, Biochemical and biophysical research communications.

[44]  Phillip M Young,et al.  Magnetic Resonance Elastography: A Novel Technique for the Detection of Hepatic Fibrosis and Hepatocellular Carcinoma After the Fontan Operation. , 2015, Mayo Clinic proceedings.

[45]  Sharon Gerecht,et al.  Hydrogels to model 3D in vitro microenvironment of tumor vascularization. , 2014, Advanced drug delivery reviews.

[46]  V. Kosma,et al.  Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer. , 1998, Cancer research.

[47]  V. Kosma,et al.  Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate , 1999, British Journal of Cancer.

[48]  Michelle R. Dawson,et al.  The malignancy of metastatic ovarian cancer cells is increased on soft matrices through a mechanosensitive Rho–ROCK pathway , 2014, Journal of Cell Science.

[49]  S. Hautmann,et al.  Bladder tumor markers for monitoring recurrence and screening comparison of hyaluronic acid–hyaluronidase and BTA‐Stat tests , 2002, Cancer.

[50]  Christopher S. Chen,et al.  Matrix rigidity regulates a switch between TGF-β1–induced apoptosis and epithelial–mesenchymal transition , 2012, Molecular biology of the cell.

[51]  G. Dubini,et al.  Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation , 2014, Proceedings of the National Academy of Sciences.

[52]  D. Discher,et al.  Fractal Heterogeneity in Minimal Matrix Models of Scars Modulates Stiff-Niche Stem-Cell Responses Via Nuclear Exit of a Mechanorepressor , 2016 .

[53]  Yang-Kao Wang,et al.  Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing , 2015, Oncotarget.

[54]  Dan H. Moore,et al.  Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer , 2007 .

[55]  Sanjay Kumar,et al.  CD44-Mediated Adhesion to Hyaluronic Acid Contributes to Mechanosensing and Invasive Motility , 2014, Molecular Cancer Research.

[56]  P. Janmey,et al.  Hepatic stellate cells require a stiff environment for myofibroblastic differentiation. , 2011, American journal of physiology. Gastrointestinal and liver physiology.

[57]  David L. Wilson,et al.  MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent , 2015, Nature Communications.

[58]  A. Papavassiliou,et al.  Polycystin‐1 and polycystin‐2 are involved in the acquisition of aggressive phenotypes in colorectal cancer , 2015, International journal of cancer.

[59]  Albert C. Chen,et al.  Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway , 2015, Nature Cell Biology.

[60]  Sharon Gerecht,et al.  Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting. , 2014, Biomaterials science.

[61]  D. Mizuno,et al.  High-resolution microrheology in the pericellular matrix of prostate cancer cells , 2012, Journal of The Royal Society Interface.

[62]  J. Erler,et al.  AGE‐modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival , 2015, The Journal of pathology.

[63]  Albert J. Keung,et al.  Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression , 2010, Molecular Cancer.

[64]  C. Ricciardelli,et al.  Role of Versican, Hyaluronan and CD44 in Ovarian Cancer Metastasis , 2011, International journal of molecular sciences.