Reticulated hyaluronan hydrogels: a model for examining cancer cell invasion in 3D

David, Laurent; Dulong, Virginie; Cerf, Didier Le; Chauzy, Claude; Norris, Victor; Delpech, Bertrand; Lamacz, Marek; Vannier, Jean‐Pierre

doi:10.1016/j.matbio.2004.05.005

Cited by 56 publications

(35 citation statements)

References 43 publications

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“…The matrices composed of collagen, fibrin, or hyaluronan represent the major matrix environments where angiogenic or vasculogenic events take place, acting as scaffold proteins for vessel formation (Davis et al, 2002;Yang et al, 2004). Of note, hyaluronan, a core component of ECM is known to contribute to the invasiveness of certain types of cancers (David et al, 2004). In the present study, the ability of Met-F-AEA to inhibit tumorinduced angiogenesis was examined in vitro using a threedimensional assay.…”

Section: Discussionmentioning

confidence: 94%

Antiangiogenic activity of the endocannabinoid anandamide: Correlation to its tumor‐suppressor efficacy

Pisanti

Borselli

Oliviero

et al. 2006

Journal Cellular Physiology

100

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Endocannabinoids are now emerging as suppressors of key cell-signaling pathways involved in cancer cell growth, invasion, and metastasis. We have previously observed that the metabolically stable anandamide analog, 2-methyl-2'-F-anandamide (Met-F-AEA) can inhibit the growth of thyroid cancer in vivo. Our hypothesis was that the anti-tumor effect observed could be at least in part ascribed to inhibition of neo-angiogenesis. Therefore, the aim of this study was to assess the anti-angiogenic activity of Met-F-AEA, to investigate the molecular mechanisms underlying this effect and whether Met-F-AEA could antagonize tumor-induced endothelial cell sprouting. We show that Met-F-AEA inhibited bFGF-stimulated endothelial cell proliferation, in a dose-dependent manner, and also induced apoptosis, both effects reliant on cannabinoid CB1 receptor stimulation. Analyzing the signaling pathways implicated in angiogenesis, we observed that the bFGF-induced ERK phosphorylation was antagonized by Met-F-AEA, and we found that p38 MAPK was involved in Met-F-AEA-induced apoptosis. Moreover, Met-F-AEA was able to inhibit bi-dimensional capillary-like tube formation and activity of matrix metalloprotease MMP-2, a major matrix degrading enzyme. Importantly, we demonstrated that Met-F-AEA is also functional in vivo since it inhibited angiogenesis in the chick chorioallantoic neovascularization model. Finally, Met-F-AEA inhibited tumor-induced angiogenesis in a three-dimensional model of endothelial and thyroid tumor cell (KiMol) spheroids co-cultures in different 3-D polymeric matrices that resemble tumor microenvironment and architecture. Thus, our results suggest that anandamide could be involved in the control of cancer growth targeting both tumor cell proliferation and the angiogenic stimulation of the vasculature.

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Section: Discussionmentioning

confidence: 94%

Antiangiogenic activity of the endocannabinoid anandamide: Correlation to its tumor‐suppressor efficacy

Pisanti

Borselli

Oliviero

et al. 2006

Journal Cellular Physiology

100

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“…However, the observed differences in invasion may also be due to differences in HA-specific interactions across cell lines, such as varying expression of CD44 [86] or hyaluronidases [87]. Indeed, the ability of tumor cell lines to invade and colonize HA hydrogels has been correlated with the expression of hyaluronidase [88], which can decrease steric barriers to invasion by degrading the matrix [89]. The two human GBM cell lines used in this study (U373-MG and U87-MG) have been reported to express certain hyaluronidases at levels that are either very low [90] or close to zero [49].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform

2011

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Glioblastoma multiforme (GBM) is a malignant brain tumor characterized by diffuse infiltration of single cells into the brain parenchyma, which is a process that relies in part on aberrant biochemical and biophysical interactions between tumor cells and the brain extracellular matrix (ECM). A major obstacle to understanding ECM regulation of GBM invasion is the absence of model matrix systems that recapitulate the distinct composition and physical structure of brain ECM while allowing independent control of adhesive ligand density, mechanics, and microstructure. To address this need, we synthesized brain-mimetic ECMs based on hyaluronic acid (HA) with a range of stiffnesses that encompasses normal and tumorigenic brain tissue and functionalized these materials with short Arg-Gly-Asp (RGD) peptides to facilitate cell adhesion. Scanning electron micrographs of the hydrogels revealed a dense, sheet-like microstructure with apparent nanoscale porosity similar to brain extracellular space. On flat hydrogel substrates, glioma cell spreading area and actin stress fiber assembly increased strongly with increasing density of RGD peptide. Increasing HA stiffness under constant RGD density produced similar trends and increased the speed of random motility. In a three-dimensional (3D) spheroid paradigm, glioma cells invaded HA hydrogels with morphological patterns distinct from those observed on flat surfaces or in 3D collagen-based ECMs but highly reminiscent of those seen in brain slices. This material system represents a brain-mimetic model ECM with tunable ligand density and stiffness amenable to investigations of the mechanobiological regulation of brain tumor progression.

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“…Using adipic acid dihydrazide-crosslinked HA hydrogels, David et al investigated the invasive behaviors of a total of thirteen different cancer cell lines (from primary tumor or metastases) (David et al, 2004). Similar to our observations, the invasiveness of the cancer cell is related to its production of hyaluronidase, the expression of HA binding receptors and the cellular secretion of HA.…”

Section: Matrix-assisted Assembly Of 3d Tumor Modelsmentioning

confidence: 99%

Three-dimensional in vitro tumor models for cancer research and drug evaluation

Farach-Carson

Jia

2014

Biotechnology Advances

401

294

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Cancer occurs when cells acquire genomic instability and inflammation, produce abnormal levels of epigenetic factors/proteins and tumor suppressors, reprogram the energy metabolism and evade immune destruction, leading to the disruption of cell cycle/normal growth. An early event in carcinogenesis is loss of polarity and detachment from the natural basement membrane, allowing cells to form distinct three-dimensional (3D) structures that interact with each other and with the surrounding microenvironment. Although valuable information has been accumulated from traditional in vitro studies in which cells are grown on flat and hard plastic surfaces (2D culture), this culture condition does not reflect the essential features of tumor tissues. Further, fundamental understanding of cancer metastasis cannot be obtained readily from 2D studies because they lack the complex and dynamic cell-cell communications and cell-matrix interactions that occur during cancer metastasis. These shortcomings, along with lack of spatial depth and cell connectivity, limit the applicability of 2D cultures to accurate testing of pharmacologically active compounds, free or sequestered in nanoparticles. To recapitulate features of native tumor microenvironments, various biomimetic 3D tumor models have been developed to incorporate cancer and stromal cells, relevant matrix components, and biochemical and biophysical cues, into one spatially and temporally integrated system. In this article, we review recent advances in creating 3D tumor models employing tissue engineering principles. We then evaluate the utilities of these novel models for the testing of anticancer drugs and their delivery systems. We highlight the profound differences in responses from 3D in vitro tumors and conventional monolayer cultures. Overall, strategic integration of biological principles and engineering approaches will both improve understanding of tumor progression and invasion and support discovery of more personalized first line treatments for cancer patients.

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Reticulated hyaluronan hydrogels: a model for examining cancer cell invasion in 3D

Cited by 56 publications

References 43 publications

Antiangiogenic activity of the endocannabinoid anandamide: Correlation to its tumor‐suppressor efficacy

Antiangiogenic activity of the endocannabinoid anandamide: Correlation to its tumor‐suppressor efficacy

Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform

Three-dimensional in vitro tumor models for cancer research and drug evaluation

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