Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level

Rebecca L. Klank; Stacy A. Decker Grunke; Benjamin L. Bangasser; Colleen L. Forster; Matthew A. Price; Thomas J. Odde; Karen S. SantaCruz; Steven S. Rosenfeld; Peter Canoll; Eva A. Turley; James B. McCarthy; John R. Ohlfest; David J. Odde

doi:10.1016/j.celrep.2016.12.024

Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level

Rebecca L. Klank, Stacy A. Decker Grunke, Benjamin L. Bangasser, Colleen L. Forster, Matthew A. Price, Thomas J. Odde, Karen S. SantaCruz, Steven S. Rosenfeld, Peter Canoll, Eva A. Turley, James B. McCarthy, John R. Ohlfest, David J. Odde

Hematology / Oncology / Cancer Center / Breast Clinic

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

While several studies link the cell-surface marker CD44 to cancer progression, conflicting results show both positive and negative correlations with increased CD44 levels. Here, we demonstrate that the survival outcomes of genetically induced glioma-bearing mice and of high-grade human glioma patients are biphasically correlated with CD44 level, with the poorest outcomes occurring at intermediate levels. Furthermore, the high-CD44-expressing mesenchymal subtype exhibited a positive trend of survival with increased CD44 level. Mouse cell migration rates in ex vivo brain slice cultures were also biphasically associated with CD44 level, with maximal migration corresponding to minimal survival. Cell simulations suggest that cell-substrate adhesiveness is sufficient to explain this biphasic migration. More generally, these results highlight the potential importance of non-monotonic relationships between survival and biomarkers associated with cancer progression.

Original language	English (US)
Pages (from-to)	23-31
Number of pages	9
Journal	Cell reports
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2016.12.024
State	Published - Jan 3 2017

Keywords

CD44
biphasic migration
biphasic survival
glioma

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2016.12.024

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Klank, R. L., Decker Grunke, S. A., Bangasser, B. L., Forster, C. L., Price, M. A., Odde, T. J., SantaCruz, K. S., Rosenfeld, S. S., Canoll, P., Turley, E. A., McCarthy, J. B., Ohlfest, J. R., & Odde, D. J. (2017). Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level. Cell reports, 18(1), 23-31. https://doi.org/10.1016/j.celrep.2016.12.024

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title = "Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level",

abstract = "While several studies link the cell-surface marker CD44 to cancer progression, conflicting results show both positive and negative correlations with increased CD44 levels. Here, we demonstrate that the survival outcomes of genetically induced glioma-bearing mice and of high-grade human glioma patients are biphasically correlated with CD44 level, with the poorest outcomes occurring at intermediate levels. Furthermore, the high-CD44-expressing mesenchymal subtype exhibited a positive trend of survival with increased CD44 level. Mouse cell migration rates in ex vivo brain slice cultures were also biphasically associated with CD44 level, with maximal migration corresponding to minimal survival. Cell simulations suggest that cell-substrate adhesiveness is sufficient to explain this biphasic migration. More generally, these results highlight the potential importance of non-monotonic relationships between survival and biomarkers associated with cancer progression.",

keywords = "CD44, biphasic migration, biphasic survival, glioma",

author = "Klank, {Rebecca L.} and {Decker Grunke}, {Stacy A.} and Bangasser, {Benjamin L.} and Forster, {Colleen L.} and Price, {Matthew A.} and Odde, {Thomas J.} and SantaCruz, {Karen S.} and Rosenfeld, {Steven S.} and Peter Canoll and Turley, {Eva A.} and McCarthy, {James B.} and Ohlfest, {John R.} and Odde, {David J.}",

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doi = "10.1016/j.celrep.2016.12.024",

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AU - Klank, Rebecca L.

AU - Decker Grunke, Stacy A.

AU - Bangasser, Benjamin L.

AU - Forster, Colleen L.

AU - Price, Matthew A.

AU - Odde, Thomas J.

AU - SantaCruz, Karen S.

AU - Rosenfeld, Steven S.

AU - Canoll, Peter

AU - Turley, Eva A.

AU - McCarthy, James B.

AU - Ohlfest, John R.

AU - Odde, David J.

PY - 2017/1/3

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N2 - While several studies link the cell-surface marker CD44 to cancer progression, conflicting results show both positive and negative correlations with increased CD44 levels. Here, we demonstrate that the survival outcomes of genetically induced glioma-bearing mice and of high-grade human glioma patients are biphasically correlated with CD44 level, with the poorest outcomes occurring at intermediate levels. Furthermore, the high-CD44-expressing mesenchymal subtype exhibited a positive trend of survival with increased CD44 level. Mouse cell migration rates in ex vivo brain slice cultures were also biphasically associated with CD44 level, with maximal migration corresponding to minimal survival. Cell simulations suggest that cell-substrate adhesiveness is sufficient to explain this biphasic migration. More generally, these results highlight the potential importance of non-monotonic relationships between survival and biomarkers associated with cancer progression.

AB - While several studies link the cell-surface marker CD44 to cancer progression, conflicting results show both positive and negative correlations with increased CD44 levels. Here, we demonstrate that the survival outcomes of genetically induced glioma-bearing mice and of high-grade human glioma patients are biphasically correlated with CD44 level, with the poorest outcomes occurring at intermediate levels. Furthermore, the high-CD44-expressing mesenchymal subtype exhibited a positive trend of survival with increased CD44 level. Mouse cell migration rates in ex vivo brain slice cultures were also biphasically associated with CD44 level, with maximal migration corresponding to minimal survival. Cell simulations suggest that cell-substrate adhesiveness is sufficient to explain this biphasic migration. More generally, these results highlight the potential importance of non-monotonic relationships between survival and biomarkers associated with cancer progression.

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Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level

Abstract

Keywords

ASJC Scopus subject areas

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