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

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

doi:10.1016/j.celrep.2017.03.074

Cited by 16 publications

(13 citation statements)

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“…Furthermore, Anido et al reported that GBM cells with high levels of CD44 have notably higher potential for developing tumors in vivo [ 24 ]. Recent studies also support the observation that CD44 may be a GBM stem cell marker in vitro and in animal models [ 15 , 20 , 25 , 26 ]. However, the molecular mechanism of GBM therapy resistance remains to be determined, and biomarkers to monitor treatment responses are in urgent need.…”

Section: Introductionsupporting

confidence: 53%

“…CD133 is one of the most commonly used markers for selecting GBM CSCs [ 15 , 18 , 19 ]. Moreover, CD44 expression in GBM cells is critical for GBM invasion and migration [ [20] , [21] , [22] , [23] ]. Furthermore, Anido et al reported that GBM cells with high levels of CD44 have notably higher potential for developing tumors in vivo [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of a panel of genes as a prognostic biomarker for glioblastoma

et al. 2018

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BackgroundGlioblastoma multiforme (GBM) is a fatal disease without effective therapy. Identification of new biomarkers for prognosis would enable more rational selections of strategies to cure patients with GBM and prevent disease relapse.MethodsSeven datasets derived from GBM patients using microarray or next generation sequencing in R2 online database (http://r2.amc.nl) were extracted and then analyzed using JMP software. The survival distribution was calculated according to the Kaplan-Meier method and the significance was determined using log-rank statistics. The sensitivity of a panel of GBM cell lines in response to temozolomide (TMZ), salinomycin, celastrol, and triptolide treatments was evaluated using MTS and tumor-sphere formation assay.FindingsWe identified that CD44, ATP binding cassette subfamily C member 3 (ABCC3), and tumor necrosis factor receptor subfamily member 1A (TNFRSF1A) as highly expressed genes in GBMs are associated with patients' poor outcomes and therapy resistance. Furthermore, these three markers combined with MGMT, a conventional GBM marker, can classify GBM patients into five new subtypes with different overall survival time in response to treatment. The four-gene signature and the therapy response of GBMs to a panel of therapeutic compounds were confirmed in a panel of GBM cell lines.InterpretationThe data indicate that the four-gene panel can be used as a therapy response index for GBM patients and potential therapeutic targets. These results provide important new insights into the early diagnosis and the prognosis for GBM patients and introduce potential targets for GBM therapeutics.FundBaylor Scott & White Health Startup Fund (E.W.); Collaborative Faculty Research Investment Program (CFRIP) of Baylor University, Baylor Scott & White Health, and Baylor College of Medicine (E.W., T.S., J.H.H.); NIH R01 NS067435 (J.H.H.); Scott & White Plummer Foundation Grant (J.H.H.); National Natural Science Foundation of China 816280007 (J.H.H. and Fu.W.).

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Section: Introductionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Identification of a panel of genes as a prognostic biomarker for glioblastoma

et al. 2018

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“…In gliomas, HA also induces the expression of several other molecules related to migration, including CD44 (cluster designation 44; HCAM, homing‐associated cell adhesion molecule; Pgp‐1, phagocytic glycoprotein‐1), PTEN (phosphatase and tensin homolog), MMPs (matrix metalloproteinases), and OPN (osteopontin; Kim et al, ; Klank et al, ; Mooney et al, ). Recently, a group of genes was identified as being differentially regulated by HA treatment.…”

Section: The Brain Extracellular Matrix and Its Interaction With Gliomentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

158

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An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process. We explore aspects of ECM interaction with glioma cells, reviewing the main glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM-binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules, and highlight the role of proteases and glycosidases in glioma infiltration; in binding and release chemokines, cytokines and growth factors; and in generating new bioactive ECM fragments. We also consider the roles of cytoskeletal signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to glioma invasion. We closely discuss therapeutic approaches based on the modulation of the extracellular matrix, targeting the control of glioma infiltration, its relative failure in clinical trials, and potential means to overcome this difficulty.

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“…Recent reports have suggested that GBM invasion is dependent on matrix HA content, [39] and survival in mice and humans depends biphasically on extracellular transmembrane CD44 levels with intermedia HA levels associated with the highest invasion potential. [40] Hence, our observed shifts in CD44 expression in GBM12 PDX cells across the hydrogels containing HA gradients suggest that this xenograft should exhibit increased invasive potential and malignancy in vivo, a conclusion borne out in vivo. [25] …”

Section: Resultsmentioning

confidence: 96%

Spatially graded hydrogels for preclinical testing of glioblastoma anticancer therapeutics

et al. 2017

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While preclinical models such as orthotopic tumors generated in mice from patient-derived specimens are widely used to predict sensitivity or therapeutic interventions for cancer, such xenografts can be slow, require extensive infrastructure, and can make in situ assessment difficult. Such concerns are heightened in highly aggressive cancers, such as glioblastoma (GBM), that display genetic diversity and short mean survival. Biomimetic biomaterial technologies offer an approach to create ex vivo models that reflect biophysical features of the tumor microenvironment (TME). We describe a microfluidic templating approach to generate spatially graded hydrogels containing patient-derived GBM cells to explore drug efficacy and resistance mechanisms.

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

Cited by 16 publications

References 0 publications

Identification of a panel of genes as a prognostic biomarker for glioblastoma

Identification of a panel of genes as a prognostic biomarker for glioblastoma

Glioma infiltration and extracellular matrix: key players and modulators

Spatially graded hydrogels for preclinical testing of glioblastoma anticancer therapeutics

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