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Shear Stress AND Cancer

Thomas A Metzger, Glen L Niebur
The mechanical environment and mechanobiology of bone marrow may play essential roles in bone adaptation, cancer metastasis, and immune cell regulation. However, the location of marrow within the trabecular pore space complicates experimental measurement of marrow mechanics. Computational models provide a means to assess the shear stress and pressure in the marrow during physiological loading, but they rely on accurate inputs for the marrow and the physics assumed for the interaction of bone and marrow. Elastic, viscoelastic, and fluid constitutive properties have all been reported from experimental measurements of marrow properties...
September 16, 2016: Journal of Biomechanics
Hui Xu, Zhongyu Li, Yaqiong Guo, Xiaojun Peng, Jianhua Qin
The development of cancer depends on a complex tissue microenvironment for sustained growth, invasion, and metastasis. The extravasation of tumor cells is a critical event in tumor metastasis. However, the process and mechanism that underlie tumor cell extravasation remain unclear, which restricts the examination of many tumor processes and presents a formidable hurdle to drug development. To explore the initial steps by which lung tumor cells interact with the brain microvascular wall in the course of extravasation, we present a simple, inexpensive, and time-saving microfluidic device to mimic the inflammatory brain microvascular microenvironment and to investigate both the biochemical and mechanical causes of lung tumor cell rolling and adhesion on inflammatory endothelium to analyze the synergistic effects on tumor extravasation under fluidic shear stress conditions...
September 9, 2016: Electrophoresis
Keri L Schadler, Nicholas J Thomas, Peter A Galie, Dong Ha Bhang, Kerry C Roby, Prince Addai, Jacob E Till, Kathleen Sturgeon, Alexander Zaslavsky, Christopher S Chen, Sandra Ryeom
Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models...
August 31, 2016: Oncotarget
Lotfi Abou-Elkacem, Katheryne E Wilson, Sadie M Johnson, Sayan M Chowdhury, Sunitha Bachawal, Benjamin J Hackel, Lu Tian, Jürgen K Willmann
Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10(th) type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer...
2016: Theranostics
Nicolas Dupont, Patrice Codogno
Autophagy is a fundamental cell biological process that controls the quality and quantity of the eukaryotic cytoplasm. Dysfunctional autophagy, when defective or excessive, has been linked to human pathologies ranging from neurodegenerative and infectious diseases to cancer and inflammatory diseases. Autophagy takes place at basal levels in all eukaryotic cells. The process is stimulated during metabolic, genotoxic, infectious, and hypoxic stress conditions and acts an adaptive mechanism essential for cell survival...
October 2016: International Journal of Biochemistry & Cell Biology
Patrícia Moura Rosa, Nimi Gopalakrishnan, Hany Ibrahim, Markus Haug, Øyvind Halaas
T cells play a central role in immunity towards cancer and infectious diseases. T cell responses are initiated in the T cell zone of the lymph node (LN), where resident antigen-bearing dendritic cells (DCs) prime and activate antigen-specific T cells passing by. In the present study, we investigated the T cell : DC interaction in a microfluidic device to understand the intercellular dynamics and physiological conditions in the LN. We show random migration of antigen-specific T cells onto the antigen-presenting DC monolayer independent of the flow direction with a mean T cell : DC dwell time of 12...
October 7, 2016: Lab on a Chip
Afu Fu, Shijun Ma, Na Wei, Blanche Xiao Xuan Tan, Ern Yu Tan, Kathy Qian Luo
Understanding the survival mechanism of metastatic cancer cells in circulation will provide new perspectives on metastasis prevention and also shed new light on metastasis-derived drug resistance. In this study, we made it feasible to detect apoptosis of circulating tumor cells (CTCs) in real-time by integrating a fluorescence resonance energy transfer (FRET)-based caspase sensor into one in vitro microfluidic circulatory system, and two in vivo models: zebrafish circulation and mouse lung metastatic model...
July 1, 2016: Oncotarget
Satoko Ishikawa, Tomoharu Miyashita, Masafumi Inokuchi, Hironori Hayashi, Katsunobu Oyama, Hidehiro Tajima, Hironori Takamura, Itasu Ninomiya, A Karim Ahmed, John W Harman, Sachio Fushida, Tetsuo Ohta
Platelets are crucial components of the tumor microenvironment that function to promote tumor progression and metastasis. In the circulation, the interaction between tumor cells and platelets increases invasiveness, protects tumor cells from shear stress and immune surveillance, and facilitates tumor cell extravasation to distant sites. However, the role and presence of platelets in the primary tumor have not been fully determined. Here, we investigated the presence of platelets around breast cancer primary tumor cells and the associations between these cells...
August 2016: Oncology Reports
Carlo Patrono
This article is part of a joint Themed section with the British Journal of Pharmacology on Targeting Inflammation to Reduce Cardiovascular Disease Risk: a Realistic Clinical Prospect? The rest of the Themed section will appear in a future issue of BJP and will be available at Prostaglandin (PG) H synthase 2 [also referred to colloquially as cyclooxygenase (COX) 2] represents a key enzyme in arachidonic acid metabolism in health and disease. It is both constitutively expressed in several human tissues (e...
October 2016: British Journal of Clinical Pharmacology
Rong Fan, Travis Emery, Yongguo Zhang, Yuxuan Xia, Jun Sun, Jiandi Wan
During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress...
2016: Scientific Reports
B Laperrousaz, L Berguiga, F E Nicolini, C Martinez-Torres, A Arneodo, V Maguer Satta, F Argoul
Cancer cell transformation is often accompanied by a modification of their viscoelastic properties. When capturing the stress-to-strain response of primary chronic myelogenous leukemia (CML) cells, from two data sets of CD34+ hematopoietic cells isolated from healthy and leukemic bone marrows, we show that the mean shear relaxation modulus increases upon cancer transformation. This stiffening of the cells comes along with local rupture events, detected as reinforced sharp local maxima of this modulus, suggesting that these cancer cells respond to a local mechanical stress by a cascade of local brittle failure events...
2016: Physical Biology
Carman K M Ip, Shan-Shan Li, Matthew Y H Tang, Samuel K H Sy, Yong Ren, Ho Cheung Shum, Alice S T Wong
One of greatest challenges to the successful treatment of cancer is drug resistance. An exciting approach is the eradication of cancer stem cells (CSCs). However, little is known about key signals regulating the formation and expansion of CSCs. Moreover, lack of a reliable predictive preclinical model has been a major obstacle to discover new cancer drugs and predict their clinical activity. Here, in ovarian cancer, a highly chemoresistant tumor that is rapidly fatal, we provide the first evidence demonstrating the causal involvement of mechanical stimulus in the CSC phenotype using a customizable microfluidic platform and three-dimensional spheroids, which most closely mimic tumor behavior...
2016: Scientific Reports
Anki Knutsson, Sabrina Hsiung, Selvi Celik, Sara Rattik, Ingrid Yao Mattisson, Maria Wigren, Howard I Scher, Jan Nilsson, Anna Hultgårdh-Nilsson
Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice...
2016: Scientific Reports
Raphael Leblanc, Olivier Peyruchaud
Platelets are essential components of hemostasis. Due to a plethora of factors released on activation, platelet functions are also connected to tumor growth, notably by acting on angiogenesis. It is now well recognized that major roles of platelets in the poor outcome of cancer patients occurs during hematogenous dissemination of cancer cells. In this review, we describe recent insights into the molecular mechanisms supporting the prometastatic activity of platelets. Platelets have been shown to promote survival of circulating tumor cells (CTCs) in the bloodstream by conferring resistance to the shear stress and attack from natural killer cells...
July 7, 2016: Blood
Diana Massai, Giuseppe Isu, Denise Madeddu, Giulia Cerino, Angela Falco, Caterina Frati, Diego Gallo, Marco A Deriu, Giuseppe Falvo D'Urso Labate, Federico Quaini, Alberto Audenino, Umberto Morbiducci
A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor...
2016: PloS One
Amélie Sabine, Cansaran Saygili Demir, Tatiana V Petrova
SIGNIFICANCE: Lymphatic vessels are important components of the cardiovascular and immune systems. They contribute both to the maintenance of normal homeostasis and to many pathological conditions, such as cancer and inflammation. The lymphatic vasculature is subjected to a variety of biomechanical forces, including fluid shear stress and vessel circumferential stretch. RECENT ADVANCES: This review will discuss recent advances in our understanding of biomechanical forces in lymphatic vessels and their role in mammalian lymphatic vascular development and function...
September 1, 2016: Antioxidants & Redox Signaling
Helmut H Popper
Metastasis in lung cancer is a multifaceted process. In this review, we will dissect the process in several isolated steps such as angiogenesis, hypoxia, circulation, and establishment of a metastatic focus. In reality, several of these processes overlap and occur even simultaneously, but such a presentation would be unreadable. Metastasis requires cell migration toward higher oxygen tension, which is based on changing the structure of the cell (epithelial-mesenchymal transition), orientation within the stroma and stroma interaction, and communication with the immune system to avoid attack...
March 2016: Cancer Metastasis Reviews
Mark K Farrugia, Daniel B Vanderbilt, Mohamad A Salkeni, J Michael Ruppert
Tumor cells inherit from their normal precursors an extensive stress response machinery that is critical for survival in response to challenges including oxidative stress, wounding, and shear stress. Kruppel-like transcription factors, including KLF4 and KLF5, are rarely affected by genetic alteration during tumorigenesis, but compose key components of the stress response machinery in normal and tumor cells and interact with critical survival pathways, including RAS, p53, survivin, and the BCL2 family of cell death regulators...
April 1, 2016: Cancer Research
Hong Yang, Liuyuan Guan, Shun Li, Ying Jiang, Niya Xiong, Li Li, Chunhui Wu, Hongjuan Zeng, Yiyao Liu
Cancer cells are subjected to fluid shear stress during passage through the venous and lymphatic system. Caveolin-1 (Cav-1), a principal structural component of caveolar membrane domains, contributes to cancer development but its mechanobiological roles under low shear stress (LSS) conditions remain largely unknown. Here, we identified Cav-1 is mechanosensitive to LSS exposure, and its activation-induced PI3K/Akt/mTOR signaling promotes motility, invadopodia formation and metastasis of breast carcinoma MDA-MB-231 cells...
March 29, 2016: Oncotarget
Adrianne Spencer, Aaron B Baker
The kinetics of receptor-mediated cell adhesion to extracellular matrix and adherent cell monolayers plays a key role in many physiological and pathological processes including cancer metastasis. Within this process the presence of fluidic shear forces is a key regulator of binding equilibrium and kinetics of cell adhesion. Current techniques to examine the kinetics of cell adhesion are either performed in the absence of flow or are low throughput, limiting their application to pharmacological compound screening or the high throughput investigation of biological mechanisms...
2016: Scientific Reports
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