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Shear Stress AND Cancer

Josette M Northcott, Ivory S Dean, Janna K Mouw, Valerie M Weaver
The tumor microenvironment is a dynamic landscape in which the physical and mechanical properties evolve dramatically throughout cancer progression. These changes are driven by enhanced tumor cell contractility and expansion of the growing tumor mass, as well as through alterations to the material properties of the surrounding extracellular matrix (ECM). Consequently, tumor cells are exposed to a number of different mechanical inputs including cell-cell and cell-ECM tension, compression stress, interstitial fluid pressure and shear stress...
2018: Frontiers in Cell and Developmental Biology
Joyjyoti Das, Somnath Maji, Tarun Agarwal, Suman Chakraborty, Tapas K Maiti
During metastatic dissemination, cancer cells experience shear stresses in narrow confinements of in vivo vasculature. Such stresses are currently known to influence a gamut of cellular processes. While a host of cells emanating from a primary tumor perish in circulation due to shear, some cells manage to migrate to distant niches and form secondary tumors. Current research focuses on how cancer cells avert such mechanical stresses and adapt themselves in order to survive. This study deals with the autophagic response of cervical cancer cells HeLa and its subline HeLa 229, exposed to physiological shear stresses in vitro, and evaluates its role as a pro-survival mechanism...
March 13, 2018: Clinical & Experimental Metastasis
Francesc Castro-Giner, Manuel C Scheidmann, Nicola Aceto
Circulating tumor cells (CTCs) are defined as those cells that detach from a cancerous lesion and enter the bloodstream. While generally most CTCs are subjected to high shear stress, anoikis signals, and immune attack in the circulatory system, few are able to survive and reach a distant organ in a viable state, possibly leading to metastasis formation. A large number of studies, both prospective and retrospective, have highlighted the association between CTC abundance and bad prognosis in patients with various cancer types...
2018: Frontiers in Medicine
Donald A Belcher, Julia A Ju, Jin Hyen Baek, Ayla Yalamanoglu, Paul W Buehler, Daniele M Gilkes, Andre F Palmer
A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (<20 mm Hg) may be increased, while O2 offloading at high O2 tensions (>20 mm Hg) is facilitated with tense (T) state PolyhHb...
2018: PloS One
Alessandro Marturano-Kruik, Michele Maria Nava, Keith Yeager, Alan Chramiec, Luke Hao, Samuel Robinson, Edward Guo, Manuela Teresa Raimondi, Gordana Vunjak-Novakovic
Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone...
February 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Boyuan Liu, Suyue Han, Brandon P Hedrick, Yahya Modarres-Sadeghi, Maureen E Lynch
Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical cues in the skeleton are an important microenvironmental parameter that modulate tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. We focused on interstitial fluid flow based on its well-known role in bone remodeling and in primary breast cancer...
December 26, 2017: Biotechnology and Bioengineering
Yu-Hsiang Lee, Chien-Hsuan Yeh
High glucose has been known to play a pathogenic role in the development and progression of bladder cancer in diabetics, whereas the leading cause of death in such patients is mainly attributed to hyperglycemia-enhanced metastasis. In addition to the impact of glucose, cancer cells may be affected by laminar shear stress (LSS) generated from interstitial, blood, and/or lymphatic fluid flows during metastasis. Although the effect of flow-induced mechanical force on cancer pathophysiology has been extensively investigated, very little is understood regarding the cells that are simultaneously stimulated by LSS and hyperglycemia...
December 22, 2017: In Vitro Cellular & Developmental Biology. Animal
William Evans
Positive cancer patient outcomes, including increased time to recurrent events, have been associated with increased counts and function of natural killer (NK) cells. NK cell counts and function are elevated following acute exercise, and the generally accepted mechanism of increased recruitment suggests that binding of epinephrine releases NK cells from endothelial tissue via decreases in adhesion molecules following. I propose that blood flow-induced shear stress may also play a role in NK cell recruitment from the endothelium...
November 2017: Medical Hypotheses
Hyun Jung Lee, Adesuwa Ewere, Miguel F Diaz, Pamela L Wenzel
Physical forces associated with tumor growth and drainage alter cancer cell invasiveness and metastatic potential. We previously showed that fluid frictional force, or shear stress, typical of lymphatic flow induces YAP1/TAZ activation in prostate cancer cells to promote motility dependent upon YAP1 but not TAZ. Here, we show that shear stress elevates TAZ protein levels and promotes TAZ nuclear localization. Increased TAZ activity drives increased DNA synthesis and induces AMOTL2, ANKRD1, and CTGF gene transcription independently of YAP1...
November 16, 2017: Cell Cycle
Xingbo Yang, Dapeng Bi, Michael Czajkowski, Matthias Merkel, M Lisa Manning, M Cristina Marchetti
Collective cell migration is a highly regulated process involved in wound healing, cancer metastasis, and morphogenesis. Mechanical interactions among cells provide an important regulatory mechanism to coordinate such collective motion. Using a self-propelled Voronoi (SPV) model that links cell mechanics to cell shape and cell motility, we formulate a generalized mechanical inference method to obtain the spatiotemporal distribution of cellular stresses from measured traction forces in motile tissues and show that such traction-based stresses match those calculated from instantaneous cell shapes...
November 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
Tori B Terrell-Hall, Mohamed Ismail Nounou, Fatema El-Amrawy, Jessica I G Griffith, Paul R Lockman
Background: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. Methods: We characterized the permeability of (125)I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model...
October 13, 2017: Oncotarget
Alexandra Muñoz, Will J Eldridge, Nina Munkholt Jakobsen, Helle Sørensen, Adam Wax, Max Costa
Cancer cells consistently exhibit decreased stiffness, however the onset and progression of this change has not been characterized. To study the development of cell stiffness changes we evaluated the shear stiffness of populations of cells during transformation to a carcinogenic state. Bronchial epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage independent growth...
October 24, 2017: Carcinogenesis
Ganesh Thiagarajan, Bruno Vizcarra, Venkata Bodapudi, Rachel Reed, Rasoul Seyedmahmoud, Yong Wang, Jeffrey P Gorski, Mary P Walker
The objectives of this project were to use finite element methods to determine how changes in the elastic modulus due to oral cancer therapeutic radiation alter the distribution of mechanical stresses in teeth and to determine if observed failures in irradiated teeth correlate with changes in mechanical stresses. A thin slice section finite element (FE) model was constructed from micro CT sections of a molar tooth using MIMICS and 3-Matic software. This model divides the tooth into three enamel regions, the dentin-enamel junction (DEJ) and dentin...
November 2017: Computer Methods in Biomechanics and Biomedical Engineering
Nuno M Oliveira, Rui L Reis, João F Mano
Biological tissues are recurrently exposed to several dynamic mechanical forces that influence cell behavior. On this work, the focus is on the shear stress forces induced by fluid flow. The study of flow-induced effects on cells leads to important advances in cardiovascular, cancer, stem cell, and bone biology understanding. These studies are performed using cell culture flow (CCF) systems, mainly parallel plate flow chambers (PPFC), and microfluidic systems. Here, it is proposed an original CCF system based on the open fluidics concept...
October 16, 2017: Advanced Healthcare Materials
Tito Panciera, Luca Azzolin, Michelangelo Cordenonsi, Stefano Piccolo
A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behaviour. Moreover, at the macroscopic scale, the influence of forces, such as the forces generated by blood flow, muscle contraction, gravity and overall tissue rigidity (for example, inside of a tumour lump), is central to our understanding of physiology and disease pathogenesis. Still, how mechanical cues are sensed and transduced at the molecular level to regulate gene expression has long remained enigmatic...
December 2017: Nature Reviews. Molecular Cell Biology
Corinna Bingel, Emily Koeneke, Johannes Ridinger, Annika Bittmann, Martin Sill, Heike Peterziel, Jagoda K Wrobel, Inga Rettig, Till Milde, Uta Fernekorn, Frank Weise, Andreas Schober, Olaf Witt, Ina Oehme
Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g., via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions...
August 24, 2017: Cell Death & Disease
M D Basson, B Zeng, S Wang
Increased extracellular pressure or shear stress activate a complex signal pathway that stimulates integrin binding affinity and potentiates metastatic cell adhesion. Inhibiting either focal adhesion kinase (FAK) and Akt1 can block this pathway, but risks interfering with the diverse other functions of each kinase. However, the mechanotransduced signal pathway involves a novel Akt1-FAK interaction not required for most FAK or Akt1 function, so modeling and blocking this interaction seems a desirable target...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Siddarth Rawal, Zheng Ao, Ram H Datar, Ashutosh Agarwal
Microfilters with slot-pore geometry can be used for size-based capture of circulating tumor cells (CTC) from the blood of cancer patients. The slot pore geometry reduces the shear stress that the cells would typically experience during filtration process and allows the cells to remain viable. The microfilter provides a platform capable of high CTC capture efficiency; however, the release of these cells from the filter following capture is nontrivial, possibly due to the strong nonspecific electrostatic adhesion of CTC to the microfilter surface...
2017: Methods in Molecular Biology
Lingxia Guo, Yuchen Shi, Xiangfei Liu, Zhitao Han, Zhenjie Zhao, Yong Chen, Wenhui Xie, Xin Li
Nanostructure-enhanced detection is promising for a number of applications such as early cancer diagnosis, environmental monitoring and mine safety, among which nanostructures integrated microfluidic chips offers unique advantage of ultra-low quantitative analyses. Here, dense ZnO nanowires of varied diameter and length were obtained by changing the content of polyethyleneimine (PEI) and growth time via simple hydrothermal growth in microfluidic channels for protein detection. We showed that this approach was superiorly efficient compared to the conventional hydrothermal method due to the flow-induced replenishment of nutrient and the effect of shear stress...
August 3, 2017: Biosensors & Bioelectronics
Sara G Mina, Peter Huang, Bruce T Murray, Gretchen J Mahler
Tumor development is influenced by stromal cells in aspects including invasion, growth, angiogenesis, and metastasis. Activated fibroblasts are one group of stromal cells involved in cancer metastasis, and one source of activated fibroblasts is endothelial to mesenchymal transformation (EndMT). EndMT begins when the endothelial cells delaminate from the cell monolayer, lose cell-cell contacts, lose endothelial markers such as vascular endothelial-cadherin (VE-cadherin), gain mesenchymal markers like alpha-smooth muscle actin (α-SMA), and acquire mesenchymal cell-like properties...
July 2017: Biomicrofluidics
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