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Title:
Acid treatment of melanoma cells selects for invasive phenotypes | Clinical & Experimental Metastasis
Description:
Solid tumors become acidic due to hypoxia and upregulated glycolysis. We have hypothesized that this acidosis leads to more aggressive invasive behavior during carcinogenesis (Nature Reviews Cancer 4:891–899, 2004). Previous work on this subject has shown mixed results. While some have observed an induction of metastasis and invasion with acid treatments, others have not. To investigate this, human melanoma cells were acclimated to low pH growth conditions. Significant cell mortality occurred during acclimation, suggesting that acidosis selected for resistant phenotypes. Cells maintained under acidic conditions exhibited a greater range of motility, a reduced capacity to form flank tumors in SCID mice and did not invade more rapidly in vitro, compared to non-selected control cells. However, re-acclimation of these selected cells to physiological pH gave rise to stable populations with significantly higher in vitro invasion. These re-acclimated cells maintained higher invasion and higher motility for multiple generations. Transcriptomic analyses of these three phenotypes revealed significant differences, including upregulation of relevant pathways important for tissue remodeling, cell cycle control and proliferation. These results reinforce the hypothesis that acidosis promotes selection of stable, more invasive phenotypes, rather than inductive changes, which would be reversible.
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article, google, scholar, cas, pubmed, cells, cancer, cell, melanoma, metastasis, acidic, invasion, gillies, tumor, usa, content, invasive, phenotypes, robert, tumors, privacy, cookies, research, acidosis, human, access, apoptosis, data, publish, search, experimental, february, moellering, krishnamurty, gatenby, nature, motility, expression, med, carcinoma, res, exp, author, information, log, journal, acid, raymond, black, hypoxia,
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month download article/chapter nih r01 ca093650 membrane-type matrix metalloproteinases urokinase-type plasminogen activator dll4-notch-hey2 signaling high-resolution measurements reveal full article pdf acidosis promotes selection experimental metastatic potential melanoma cells selects c8161 melanoma cells privacy choices/manage cookies cell cycle control carcinoma cell lines arterial cell fate acid treatment human melanoma cells arizona cancer center related subjects upregulating mmp family acidic conditions exhibited form flank tumors acidic ph enhances murine tumour cells endothelial progenitor cells hepatocellular carcinoma cells mb-mda-231 cells breast cancer cells conditions privacy policy european economic area relevant pathways important increased exosome release increasing caspase activity van muijen gnp automatic lesion tracking fulmer-smentek sb robust local normalization high aerobic glycolysis electronic supplementary material quantitative fluorescent tracking reaction-diffusion model selected control cells shown mixed results p53-dependent transactivation athymic nude mice acidic environment leads malignant cells ovarian carcinoma cells article log aggressive invasive behavior
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- Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis?
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headline:Acid treatment of melanoma cells selects for invasive phenotypes
description:Solid tumors become acidic due to hypoxia and upregulated glycolysis. We have hypothesized that this acidosis leads to more aggressive invasive behavior during carcinogenesis (Nature Reviews Cancer 4:891–899, 2004). Previous work on this subject has shown mixed results. While some have observed an induction of metastasis and invasion with acid treatments, others have not. To investigate this, human melanoma cells were acclimated to low pH growth conditions. Significant cell mortality occurred during acclimation, suggesting that acidosis selected for resistant phenotypes. Cells maintained under acidic conditions exhibited a greater range of motility, a reduced capacity to form flank tumors in SCID mice and did not invade more rapidly in vitro, compared to non-selected control cells. However, re-acclimation of these selected cells to physiological pH gave rise to stable populations with significantly higher in vitro invasion. These re-acclimated cells maintained higher invasion and higher motility for multiple generations. Transcriptomic analyses of these three phenotypes revealed significant differences, including upregulation of relevant pathways important for tissue remodeling, cell cycle control and proliferation. These results reinforce the hypothesis that acidosis promotes selection of stable, more invasive phenotypes, rather than inductive changes, which would be reversible.
datePublished:2008-02-27T00:00:00Z
dateModified:2008-02-27T00:00:00Z
pageStart:411
pageEnd:425
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Acid–base
Melanoma
Evolution
Invasion
Motility
Cancer Research
Biomedicine
general
Oncology
Hematology
Surgical Oncology
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headline:Acid treatment of melanoma cells selects for invasive phenotypes
description:Solid tumors become acidic due to hypoxia and upregulated glycolysis. We have hypothesized that this acidosis leads to more aggressive invasive behavior during carcinogenesis (Nature Reviews Cancer 4:891–899, 2004). Previous work on this subject has shown mixed results. While some have observed an induction of metastasis and invasion with acid treatments, others have not. To investigate this, human melanoma cells were acclimated to low pH growth conditions. Significant cell mortality occurred during acclimation, suggesting that acidosis selected for resistant phenotypes. Cells maintained under acidic conditions exhibited a greater range of motility, a reduced capacity to form flank tumors in SCID mice and did not invade more rapidly in vitro, compared to non-selected control cells. However, re-acclimation of these selected cells to physiological pH gave rise to stable populations with significantly higher in vitro invasion. These re-acclimated cells maintained higher invasion and higher motility for multiple generations. Transcriptomic analyses of these three phenotypes revealed significant differences, including upregulation of relevant pathways important for tissue remodeling, cell cycle control and proliferation. These results reinforce the hypothesis that acidosis promotes selection of stable, more invasive phenotypes, rather than inductive changes, which would be reversible.
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Melanoma
Evolution
Invasion
Motility
Cancer Research
Biomedicine
general
Oncology
Hematology
Surgical Oncology
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