The role of CD44 in glioblastoma multiforme

Mooney, Kelly L.; Choy, Winward; Sidhu, Sabrin; Pelargos, Panayiotis; Bui, Timothy T.; Voth, Brittany; Barnette, Natalie E.; Yang, Isaac

doi:10.1016/j.jocn.2016.05.012

Cited by 132 publications

(107 citation statements)

References 63 publications

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“…CD44 has been shown to be a representative marker of the mesenchymal subtype of GBM 36–38 . We therefore used CD44 IHC as a surrogate of a mesenchymal phenotype of GBM to characterize our tumor models.…”

Section: Resultsmentioning

confidence: 99%

“…S1). TGF-β signaling pathway has been implicated in epithelial-to-mesenchymal transition (EMT) in cancer 16, 39, 40 and mesenchymal GBM 38 . RT-PCR analysis of TGF-β1, 2, and TβRII showed a tendency toward increased expression of these components of the TGF-β signaling pathway in our recGSC lines compared with newly diagnosed GSCs in vitro (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…CD44 has been shown to be a representative marker of the mesenchymal subtype of GBM. [36][37][38] We therefore used CD44 IHC as a surrogate of a mesenchymal phenotype of GBM to characterize our tumor models. Tumor cells were strongly immunopositive for CD44 in all the recGBM models tested, while the newly diagnosed GSC xenograft of the proneural subtype (MGG8) was negative ( Fig.…”

Section: Mesenchymal-like Phenotype and Activated Tgf-b Pathway In Rementioning

confidence: 99%

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Blockade of transforming growth factor‐β signaling enhances oncolytic herpes simplex virus efficacy in patient‐derived recurrent glioblastoma models

Esaki

Nigim

Moon

et al. 2017

Intl Journal of Cancer

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Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis. We hypothesized that oHSV and TGF-β inhibitors would synergistically exert anti-tumor effects for recurrent GBM. Here we established a panel of patient-derived recurrent tumor models from GBMs that relapsed after post-surgical radiation and chemotherapy, based on GSC-enriched tumor sphere cultures. These GSCs are resistant to the standard-of-care temozolomide but susceptible to oHSVs G47Δ and MG18L. Inhibition of TGF-β receptor kinase with selective targeted small molecules reduced clonogenic sphere formation in all tested recurrent GSCs. The combination of oHSV and TGF-βR inhibitor was synergistic in killing recurrent GSCs through, in part, an inhibitor-induced JNK-MAPK blockade and increase in oHSV replication. In vivo, systemic treatment with TGF-βR inhibitor greatly enhanced the anti-tumor effects of single intratumoral oHSV injections, resulting in cures in 60% of mice bearing orthotopic recurrent GBM. These results reveal a novel synergistic interaction of oHSV therapy and TGF-β signaling blockade, and warrant further investigations aimed at clinical translation of this combination strategy for GBM patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Mesenchymal-like Phenotype and Activated Tgf-b Pathway In Rementioning

confidence: 99%

See 1 more Smart Citation

Blockade of transforming growth factor‐β signaling enhances oncolytic herpes simplex virus efficacy in patient‐derived recurrent glioblastoma models

Esaki

Nigim

Moon

et al. 2017

Intl Journal of Cancer

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“…A promising method to actively target cancer cells is the exploitation of the differential expression of Cluster Differentiation 44 (CD44). CD44 is a cell membrane bound surface receptor that mediates cell–cell and cell‐extracellular matrix (ECM) communication (Kingsmore et al, ; Mooney et al, ) and has been found to be overexpressed in numerous cancer types including breast (Cabuk et al, ), lung (Guo et al, ), colorectal (Xia & Xu, ) tumors compared to basal expression in equivalent healthy tissue (Rios de la Rosa, Tirella, Gennari, Stratford, & Tirelli, ). Hyaluronic acid (HA), a main component of the ECM, is a natural ligand to CD44 has been used as a targeting moiety for CD44 overexpressing cancers, facilitating preferential uptake, and potent therapeutic efficacy (Orian, ).…”

Section: Introductionmentioning

confidence: 99%

Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme

Barbarisi

Iaffaioli

Armenia

et al. 2018

Journal Cellular Physiology

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Glioblastoma multiforme is the most common and aggressive primary brain cancer with only ∼3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment.

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“…In such manner radiochemoresistance may progressively evolve, particularly with relapse of the tumor. Transmembrane CD44 is overexpressed in many neoplasms and is implicated in cell motility, tumor growth and angiogenesis [13]. Non-structural apoptotic mechanisms may implicate functional inhibitory factors that augment tumor resistance to therapy.…”

Section: Microenvironmentmentioning

confidence: 99%

Dimensions of Niche-Induced Anti-Apoptosis of Therapeutically Resistant Neoplasms in Radio-Chemo-Therapy

Agius

2017

IJRRT

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It is proposed that apoptotic linear progression schemes do not adequately account for the emergence of non-response in radio-chemoresistant neoplastic lesions. In such defining contributory patterns of activated and non-activated apoptosis there is emerging evidence for distributional programs sustained by networks of spatial distribution. Such a concept may well implicate angiogenic switches and origins of vessels and tumor cells from a resident stem cell population in the niche micro-environment. It is towards the realization of performance attributes of cell-cycle arrest on the one hand and of proliferative dysfunctionality that the resistance and relapse of tumors is exemplified by an integrated clonogenic phenomenon of cellular derivation and end-result as relapsed neoplasms.

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The role of CD44 in glioblastoma multiforme

Cited by 132 publications

References 63 publications

Blockade of transforming growth factor‐β signaling enhances oncolytic herpes simplex virus efficacy in patient‐derived recurrent glioblastoma models

Blockade of transforming growth factor‐β signaling enhances oncolytic herpes simplex virus efficacy in patient‐derived recurrent glioblastoma models

Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme

Dimensions of Niche-Induced Anti-Apoptosis of Therapeutically Resistant Neoplasms in Radio-Chemo-Therapy

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