Glioblastoma Behaviors in Three-Dimensional Collagen-Hyaluronan Composite Hydrogels

Rao, Shreya; DeJesus, Jessica; Short, Aaron R.; Otero, José; Sarkar, Atom; Winter, Jessica O.

doi:10.1021/am402097j

Cited by 139 publications

(133 citation statements)

References 64 publications

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“…Primary cells from glioma patient tumor material exposed to increasing concentrations of HA responded with rounded morphology and reduced migration, suggesting that HA concentrations may affect glioma cell behavior. [62] Consistently, addition of HA to porous chitosan scaffolds [63] or to artificial hydrogels [64] increased the expression of stem cell markers and VEGF and HIF-1, respectively. However, the finding that increasing matrix stiffness -by adding agarose to a collagen I matrix -blocks glioma invasiveness, [19] suggested that stiffness alone and independent of ligand binding acted as a critical determinant for primary brain tumor cell function.…”

Section: The Impact Of the Embedding Matrix On The Behavior Of The Tumentioning

confidence: 85%

Dissecting brain tumor growth and metastasis in vitro and ex vivo

Grotzer¹,

Neve²,

Baumgärtner³

2016

JCMT

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Local infiltration and distal dissemination of tumor cells hamper efficacy of current treatments against central nervous system (CNS) tumors and greatly influence mortality and therapy-induced longterm morbidity in survivors. A number of in vitro and ex vivo assay systems have been established to better understand the infiltration and metastatic processes, to search for molecules that specifically block tumor cell infiltration and metastatic dissemination and to pre-clinically evaluate their efficaciousness. These systems allow analytical testing of tumor cell viability and motile and invasive capabilities in simplified and well-controlled environments. However, the urgent need for novel anti-metastatic therapies has provided an incentive for the further development of not only classical in vitro methods but also of novel, physiologically more relevant assay systems including organotypic brain slice culture. In this review, using publicly available peer-reviewed primary research and review articles, we provide an overview of a selection of in vitro and ex vivo techniques widely used to study growth and dissemination of primary metastatic brain tumors. Furthermore, we discuss how our steadily increasing knowledge of tumor biology and the tumor microenvironment could be integrated to improve current research methods for metastatic brain tumors. We believe that such rationally improved methods will ultimately increase our understanding of the biology of brain tumors and facilitate the development of more efficacious anti-metastatic treatments. Local infiltration and distal dissemination of tumor cells hamper efficacy of current treatments against central nervous system (CNS) tumors and greatly influence mortality and therapy-induced long-term morbidity in survivors. A number of in vitro and ex vivo assay systems have been established to better understand the infiltration and metastatic processes, to search for molecules that specifically block tumor cell infiltration and metastatic dissemination and to pre-clinically evaluate their efficaciousness. These systems allow analytical testing of tumor cell viability and motile and invasive capabilities in simplified and well-controlled environments. However, the urgent need for novel anti-metastatic therapies has provided an incentive for the further development of not only classical in vitro methods but also of novel, physiologically more relevant assay systems including organotypic brain slice culture. In this review, using publicly available peer-reviewed primary research and review articles, we provide an overview of a selection of in vitro and ex vivo techniques widely used to study growth and dissemination of primary metastatic brain tumors. Furthermore, we discuss how our steadily increasing knowledge of tumor biology and the tumor microenvironment could be integrated to improve current research methods for metastatic brain tumors. We believe that such rationally improved methods will ultimately increase our understanding of the biology of brain tumors ...

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Section: The Impact Of the Embedding Matrix On The Behavior Of The Tumentioning

confidence: 85%

Dissecting brain tumor growth and metastasis in vitro and ex vivo

Grotzer¹,

Neve²,

Baumgärtner³

2016

JCMT

View full text Add to dashboard Cite

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“…Rao et al used composite hydrogels comprising mixtures of type I collagen and thiolated hyaluronic acid to examine the effects of ECM composition on primary human glioblastoma-derived cell motility. [61] They found that higher concentrations of hyaluronic acid correlated with a slower migration speed and more rounded cell morphology, as well as a higher elastic modulus of the gels. [61] The Harley group has utilized hydrogels comprising a combination GelMA, acrylated PEG, and methacrylated hyaluronic acid crosslinked via radical-initiated chain polymerization.…”

Section: Biomaterials For 3d Cell Biology Prospective Articlementioning

confidence: 97%

“…[61] They found that higher concentrations of hyaluronic acid correlated with a slower migration speed and more rounded cell morphology, as well as a higher elastic modulus of the gels. [61] The Harley group has utilized hydrogels comprising a combination GelMA, acrylated PEG, and methacrylated hyaluronic acid crosslinked via radical-initiated chain polymerization. [62][63][64] In one study, they found that increasing the relative amount of hyaluronic acid in the gel induced U87 glioblastoma cells to increase expression of genes associated with malignancy, including the angiogenic factor VEGF and the hypoxia marker HIF-1.…”

Section: Biomaterials For 3d Cell Biology Prospective Articlementioning

confidence: 97%

Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics

2017

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Tissue engineering holds great promise for advancing cancer research and achieving the goals of the Cancer Moonshot by providing better models for basic research and testing novel therapeutics. This paper focuses on the use of hydrogel biomaterials due to their unique ability to entrap cells in three-dimensional (3D) matrix that mimics tissues and can be programmed with physical and chemical cues to recreate key aspects of tumor microenvironments. The chemistry of some commonly used hydrogel platforms is discussed, and important examples of their use in tissue engineering 3D cancer models are highlighted. Challenges and opportunities for future research are also discussed.

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“…Therefore, to investigate the role of HA in GBM invasion, the HA is chemically modified so that it is cross-linked. Chemically modified forms of HA hydrogels include thiolated HA (Rao et al, 2013a), methacrylated HA (Ananthanarayanan et al, 2011;Kim and Kumar, 2014), and mixtures with GelMA . GBM cells are strongly influenced by the HA concentration and show increased invasion via CD44-mediated HA adhesion (Kim and Kumar, 2014).…”

Section: Matrices To Mimic the Ecm Componentsmentioning

confidence: 99%

“…Physical blending with other cross-linkable hydrogels, such as collagen, is another means of incorporating HA components into ECM-mimetic model system. By creating interpenetrating polymer networks with HA solution and collagen gels, HA-rich matrices can be created (Yang et al, 2011;Rao et al, 2013a;Cha et al, 2016). Within this HA-rich matric, GBM develops highly proliferative, invasive phenotypes (Cha et al, 2016).…”

Section: Matrices To Mimic the Ecm Componentsmentioning

confidence: 99%

Biomimetic Strategies for the Glioblastoma Microenvironment

Cha

Kim

2017

Front. Mater.

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Glioblastoma multiforme (GBM) is a devastating type of tumor with high mortality, caused by extensive infiltration into adjacent tissue and rapid recurrence. Most therapies for GBM have focused on the cytotoxicity and have not targeted GBM spread. However, there have been numerous attempts to improve therapy by addressing GBM invasion, through understanding and mimicking its behavior using three-dimensional (3D) experimental models. Compared with two-dimensional models and in vivo animal models, 3D GBM models can capture the invasive motility of glioma cells within a 3D environment comprising many cellular and non-cellular components. Based on tissue engineering techniques, GBM invasion has been investigated within a biologically relevant environment, from biophysical and biochemical perspectives, to clarify the pro-invasive factors of GBM. This review discusses the recent progress in techniques for modeling the microenvironments of GBM tissue and suggests future directions with respect to recreating the GBM microenvironment and preclinical applications.

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Glioblastoma Behaviors in Three-Dimensional Collagen-Hyaluronan Composite Hydrogels

Cited by 139 publications

References 64 publications

Dissecting brain tumor growth and metastasis in vitro and ex vivo

Dissecting brain tumor growth and metastasis in vitro and ex vivo

Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics

Biomimetic Strategies for the Glioblastoma Microenvironment

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