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Title:
Extracellular acidity, a “reappreciated” trait of tumor environment driving malignancy: perspectives in diagnosis and therapy | Cancer and Metastasis Reviews
Description:
Tumors are ecosystems which develop from stem cells endowed with unlimited self-renewal capability and genetic instability, under the effects of mutagenesis and natural selection imposed by environmental changes. Abnormal vascularization, reduced lymphatic network, uncontrolled cell growth frequently associated with hypoxia, and extracellular accumulation of glucose metabolites even in the presence of an adequate oxygen level are all factors contributing to reduce pH in the extracellular space of tumors. Evidence is accumulating that acidity is associated with a poor prognosis and participates actively to tumor progression. This review addresses some of the most experimental evidences providing that acidity of tumor environment facilitates local invasiveness and metastatic dissemination, independently from hypoxia, with which acidity is often but not always associated. Clinical investigations have also shown that tumors with acidic environment are associated with resistance to chemotherapy and radiation-induced apoptosis, suppression of cytotoxic lymphocytes, and natural killer cells tumoricidal activity. Therefore, new technologies for functional and molecular imaging as well as strategies directed to target low extracellular pH and low pH-adapted tumor cells might represent important issues in oncology.
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Topics {✒️}
integral molecular/biochemical/metabolic/clinical approach ph-dependent talin-actin binding connecting tgf-β signaling stromal-epithelial ‘lactate shuttle month download article/chapter g2-phase arrest caused tumor-secreted lactic acid francesca bianchini & lido calorini distinct cis-acting sequences nf-κb/il-8 pathway 18f-fdg pet/ct 1 urokinase-type plasminogen activator high-resolution measurements reveal cancer-generated lactic acid jnk/c-jun activation ph-responsive relaxometric probe nf-κb favours vegf acidic ph-induced elevation gelatinase a-deficient mice actin-filament-severing protein low-ph culture condition pro-angiogenesis factor vegf radiation-induced p53 expression ph-dependent antitumor activity tumor microenvironment abnormalities tumor-microenvironment interactions enforce tumour regression drives tumor angiogenesis privacy choices/manage cookies coronary endothelial cells metastatic phenotypic diversity acid-mediated invasion invadopodia components revealed esophageal adenocarcinoma cells explain metastatic dormancy human cervical cancers full article pdf actin-depolymerizing factor acidic stress promotes acidic melanoma cells epithelial cells decide high resolution ph proton pump inhibitors murine tumor-infiltrating natural selection imposed partially folded intermediate increases antitumor immunoreactivity lactate enhances motility hypoxia-inducible factor 1 radiation-induced apoptosis
Questions {❓}
- Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite?
- Contact interactions between cells that suppress neoplastic development: can they also explain metastatic dormancy?
- Is cancer a disease of abnormal cellular metabolism?
- Is there a role for carbohydrate restriction in the treatment and prevention of cancer?
- Protons extruded by NHE1: digestive or glue?
- Why do cancers have high aerobic glycolysis?
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headline:Extracellular acidity, a “reappreciated” trait of tumor environment driving malignancy: perspectives in diagnosis and therapy
description:Tumors are ecosystems which develop from stem cells endowed with unlimited self-renewal capability and genetic instability, under the effects of mutagenesis and natural selection imposed by environmental changes. Abnormal vascularization, reduced lymphatic network, uncontrolled cell growth frequently associated with hypoxia, and extracellular accumulation of glucose metabolites even in the presence of an adequate oxygen level are all factors contributing to reduce pH in the extracellular space of tumors. Evidence is accumulating that acidity is associated with a poor prognosis and participates actively to tumor progression. This review addresses some of the most experimental evidences providing that acidity of tumor environment facilitates local invasiveness and metastatic dissemination, independently from hypoxia, with which acidity is often but not always associated. Clinical investigations have also shown that tumors with acidic environment are associated with resistance to chemotherapy and radiation-induced apoptosis, suppression of cytotoxic lymphocytes, and natural killer cells tumoricidal activity. Therefore, new technologies for functional and molecular imaging as well as strategies directed to target low extracellular pH and low pH-adapted tumor cells might represent important issues in oncology.
datePublished:2014-07-02T00:00:00Z
dateModified:2014-07-02T00:00:00Z
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Tumor metabolism
“Warburg effect”
Extracellular acidity
Invasiveness
Metastatic dissemination
Stemness
Molecular imaging
Novel therapeutic strategies
Cancer Research
Oncology
Biomedicine
general
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description:Tumors are ecosystems which develop from stem cells endowed with unlimited self-renewal capability and genetic instability, under the effects of mutagenesis and natural selection imposed by environmental changes. Abnormal vascularization, reduced lymphatic network, uncontrolled cell growth frequently associated with hypoxia, and extracellular accumulation of glucose metabolites even in the presence of an adequate oxygen level are all factors contributing to reduce pH in the extracellular space of tumors. Evidence is accumulating that acidity is associated with a poor prognosis and participates actively to tumor progression. This review addresses some of the most experimental evidences providing that acidity of tumor environment facilitates local invasiveness and metastatic dissemination, independently from hypoxia, with which acidity is often but not always associated. Clinical investigations have also shown that tumors with acidic environment are associated with resistance to chemotherapy and radiation-induced apoptosis, suppression of cytotoxic lymphocytes, and natural killer cells tumoricidal activity. Therefore, new technologies for functional and molecular imaging as well as strategies directed to target low extracellular pH and low pH-adapted tumor cells might represent important issues in oncology.
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Tumor metabolism
“Warburg effect”
Extracellular acidity
Invasiveness
Metastatic dissemination
Stemness
Molecular imaging
Novel therapeutic strategies
Cancer Research
Oncology
Biomedicine
general
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