scholarly journals The Mechanical Microenvironment in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1452
Author(s):  
Stephen J.P. Pratt ◽  
Rachel M. Lee ◽  
Stuart S. Martin
Keyword(s):  
Breast Cancer ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Normal Breast ◽  
Interstitial Fluid Pressure ◽  
Mechanical Stimuli ◽  
Solid Stress ◽  
Physical Cues

Mechanotransduction is the interpretation of physical cues by cells through mechanosensation mechanisms that elegantly translate mechanical stimuli into biochemical signaling pathways. While mechanical stress and their resulting cellular responses occur in normal physiologic contexts, there are a variety of cancer-associated physical cues present in the tumor microenvironment that are pathological in breast cancer. Mechanistic in vitro data and in vivo evidence currently support three mechanical stressors as mechanical modifiers in breast cancer that will be the focus of this review: stiffness, interstitial fluid pressure, and solid stress. Increases in stiffness, interstitial fluid pressure, and solid stress are thought to promote malignant phenotypes in normal breast epithelial cells, as well as exacerbate malignant phenotypes in breast cancer cells.

scholarly journals Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours – In vitro and in vivo proof of concept

Ultrasonics ◽  
2014 ◽  
Vol 54 (7) ◽  
pp. 1938-1944 ◽  
Author(s):  
V.G. Halldorsdottir ◽  
J.K. Dave ◽  
J.R. Eisenbrey ◽  
P. Machado ◽  
H. Zhao ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
Proof Of Concept ◽  
Pressure Estimation

Simultaneous Measurement of Interstitial Fluid Pressure and Load in Rat Skin After Strain Application In Vitro

2003 ◽  
Vol 31 (10) ◽  
pp. 1246-1254 ◽  
Author(s):  
David M. Wright ◽  
Helge Wiig ◽  
C. Peter Winlove ◽  
Joel L. Bert ◽  
Rolf K. Reed
Keyword(s):  
Simultaneous Measurement ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Interstitial Fluid Pressure ◽  
Rat Skin

scholarly journals Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Giada Zurlo ◽  
Xijuan Liu ◽  
Mamoru Takada ◽  
Cheng Fan ◽  
Jeremy M. Simon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Protein Level ◽  
Triple Negative ◽  
Normal Breast ◽  
Cancer Subtypes ◽  
Adenylosuccinate Lyase ◽  
Non Coding Rna

AbstractProtein hydroxylation affects protein stability, activity, and interactome, therefore contributing to various diseases including cancers. However, the transiency of the hydroxylation reaction hinders the identification of hydroxylase substrates. By developing an enzyme-substrate trapping strategy coupled with TAP-TAG or orthogonal GST- purification followed by mass spectrometry, we identify adenylosuccinate lyase (ADSL) as an EglN2 hydroxylase substrate in triple negative breast cancer (TNBC). ADSL expression is higher in TNBC than other breast cancer subtypes or normal breast tissues. ADSL knockout impairs TNBC cell proliferation and invasiveness in vitro and in vivo. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. Hydroxylation-proficient ADSL, by affecting adenosine levels, represses the expression of the long non-coding RNA MIR22HG, thus upregulating cMYC protein level. Our findings highlight the role of ADSL hydroxylation in controlling cMYC and TNBC tumorigenesis.

scholarly journals The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

BMC Medicine ◽  
2010 ◽  
Vol 8 (1) ◽  
Author(s):  
Jodie M Fleming ◽  
Tyler C Miller ◽  
Mariam Quinones ◽  
Zhen Xiao ◽  
Xia Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Premenopausal Women ◽  
Normal Breast

scholarly journals The Solid Mechanics of Cancer and Strategies for Improved Therapy

2017 ◽  
Vol 139 (2) ◽  
Author(s):  
Triantafyllos Stylianopoulos
Keyword(s):  
Tumor Progression ◽  
Interstitial Fluid ◽  
Solid Mechanics ◽  
Fluid Pressure ◽  
Lymphatic Vessels ◽  
Chemotherapeutic Agents ◽  
Interstitial Fluid Pressure ◽  
Mathematical Framework ◽  
Solid Stress ◽  
Stress Levels

Tumor progression and response to treatment is determined in large part by the generation of mechanical stresses that stem from both the solid and the fluid phase of the tumor. Furthermore, elevated solid stress levels can regulate fluid stresses by compressing intratumoral blood and lymphatic vessels. Blood vessel compression reduces tumor perfusion, while compression of lymphatic vessels hinders the ability of the tumor to drain excessive fluid from its interstitial space contributing to the uniform elevation of the interstitial fluid pressure. Hypoperfusion and interstitial hypertension pose major barriers to the systemic administration of chemotherapeutic agents and nanomedicines to tumors, reducing treatment efficacies. Hypoperfusion can also create a hypoxic and acidic tumor microenvironment that promotes tumor progression and metastasis. Hence, alleviation of intratumoral solid stress levels can decompress tumor vessels and restore perfusion and interstitial fluid pressure. In this review, three major types of tissue level solid stresses involved in tumor growth, namely stress exerted externally on the tumor by the host tissue, swelling stress, and residual stress, are discussed separately and details are provided regarding their causes, magnitudes, and remedies. Subsequently, evidence of how stress-alleviating drugs could be used in combination with chemotherapy to improve treatment efficacy is presented, highlighting the potential of stress-alleviation strategies to enhance cancer therapy. Finally, a continuum-level, mathematical framework to incorporate these types of solid stress is outlined.

scholarly journals Integrin αvβ3 acts downstream of insulin in normalization of interstitial fluid pressure in sepsis and in cell-mediated collagen gel contraction

2008 ◽  
Vol 295 (2) ◽  
pp. H555-H560 ◽  
Author(s):  
Øyvind Sverre Svendsen ◽  
Åsa Lidén ◽  
Torbjørn Nedrebø ◽  
Kristofer Rubin ◽  
Rolf K. Reed
Keyword(s):  
Interstitial Fluid ◽  
Driving Forces ◽  
Fluid Pressure ◽  
Collagen Gel ◽  
Interstitial Fluid Pressure ◽  
C2c12 Cells ◽  
Insulin Administration ◽  
Edema Formation ◽  
Collagen Gel Contraction

The administration of insulin is recommended to patients with severe sepsis and hyperglycemia. Previously, we demonstrated that insulin may have direct anti-inflammatory properties and counteracted fluid losses from the circulation by normalizing the interstitial fluid pressure (PIF). PIF is one of the Starling forces determining fluid flux over the capillary wall, and a lowered PIF is one of the driving forces in early edema formation in inflammatory reactions. Here we demonstrate that insulin restores a lipopolysaccharide (LPS)-lowered PIF via a mechanism involving integrin αvβ3. In C57 black mice ( n = 6), LPS lowered PIF from −0.2 ± 0.2 to −1.6 ± 0.3 ( P < 0.05) and after insulin averaged −0.8 ± 0.2 mmHg ( P = 0.098 compared with after LPS). Corresponding values in wild-type BALB/c mice ( n = 5) were −0.8 ± 0.1, −2.1 ± 0.3 ( P < 0.05), and −0.8 ± 0.3 mmHg ( P < 0.05 compared with LPS) after insulin administration. In BALB/c integrin β3-deficient (β3−/−) mice ( n = 6), LPS lowered PIF from −0.1 ± 0.2 to −1.5 ± 0.3 mmHg ( P < 0.05). Insulin did not, however, restore PIF in these mice (averaged −1.7 ± 0.3 mmHg after insulin administration). Cell-mediated collagen gel contraction can serve as an in vitro model for in vivo measurements of PIF. Insulin induced αvβ3-integrin-dependent collagen gel contraction mediated by C2C12 cells. Our findings suggest a beneficiary effect of insulin for patients with sepsis with regard to the fluid balance, and this effect may in part be due to a normalization of PIF by a mechanism involving the integrin αvβ3.

scholarly journals Intracellular and Extracellular MicroRNAs in Breast Cancer

2011 ◽  
Vol 57 (1) ◽  
pp. 18-32 ◽  
Author(s):  
Claire Corcoran ◽  
Anne M Friel ◽  
Michael J Duffy ◽  
John Crown ◽  
Lorraine O'Driscoll
Keyword(s):  
Breast Cancer ◽  
Therapeutic Targets ◽  
Systemic Circulation ◽  
Normal Breast ◽  
Response To Treatment ◽  
In Vivo Models ◽  
Diagnosis And Prognosis ◽  
Extracellular Mirnas

BACKGROUND Successful treatment of breast cancer is enhanced by early detection and, if possible, subsequent patient-tailored therapy. Toward this goal, it is essential to identify and understand the most relevant panels of biomarkers, some of which may also have relevance as therapeutic targets. METHODS We critically reviewed published literature on microRNAs (miRNAs) as relevant to breast cancer. SUMMARY Since the initial recognition of the association of miRNAs with breast cancer in 2005, studies involving cell lines, in vivo models, and clinical specimens have implicated several functions for miRNAs, including suppressing oncogenesis and tumors, promoting or inhibiting metastasis, and increasing sensitivity or resistance to chemotherapy and targeted agents in breast cancer. For example, miR-21 is overexpressed in both male and female breast tumors compared with normal breast tissue and has been associated with advanced stage, lymph node positivity, and reduced survival time. miR-21 knock-down in cell-line models has been associated with increased sensitivity to topotecan and taxol in vitro and the limitation of lung metastasis in vivo. Furthermore, the discovery of extracellular miRNAs (including miR-21), existing either freely or in exosomes in the systemic circulation, has led to the possibility that such molecules may serve as biomarkers for ongoing patient monitoring. Although additional investigations are necessary to fully exploit the use of miRNAs in breast cancer, there is increasing evidence that miRNAs have potential not only to facilitate the determination of diagnosis and prognosis and the prediction of response to treatment, but also to act as therapeutic targets and replacement therapies.

scholarly journals High-throughput allelic expression imbalance analyses identify candidate breast cancer risk genes

2019 ◽  
Author(s):  
Mahdi Moradi Marjaneh ◽  
Haran Sivakumaran ◽  
Kristine M Hillman ◽  
Susanne Kaufmann ◽  
Nehal Hussein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regulatory Elements ◽  
Normal Breast ◽  
Allelic Expression ◽  
Allelic Expression Imbalance ◽  
Risk Genes ◽  
Causal Variants ◽  
Breast Cells

ABSTRACTFine-mapping of breast cancer GWAS regions has identified 195 high confidence signals containing more than 5,000 credible causal variants (CCVs). The CCVs are predominantly noncoding and enriched in regulatory elements and thus may confer the risk by altering gene expression in cis. We analyzed allelic expression imbalance (AEI) of genes surrounding known breast cancer signals, using normal breast and breast tumor transcriptome data and imputed genotypes. Fourteen genes, including NTN4, were identified whose expression was associated with CCV genotype. We showed that CCVs at this signal were located within an enhancer that physically interacts with the NTN4 promoter. Furthermore, knockdown of NTN4 in breast cells increased cell proliferation in vitro and tumor growth in vivo. Here, we present the most comprehensive AEI analysis of breast cancer CCVs resulting in identification of new candidate risk genes.

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