Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment

Truong, Danh D.; Puleo, Julieann; Llave, Alison; Mouneimne, Ghassan; Kamm, Roger D.; Nikkhah, Mehdi

doi:10.1038/srep34094

Cited by 116 publications

(111 citation statements)

References 72 publications

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“…F-actin cytoskeleton staining was quantified using Particle Analyzer Plugin ImageJ software, as described earlier. 14 The epithelial cell shape with large cell volume and roundness of the cell was calculated as described earlier. 15,16…”

Section: Secreted Vegf Level Estimationmentioning

confidence: 99%

Vitamin-D3 (α-1, 25(OH) 2D3) Protects Retinal Pigment Epithelium From Hyperoxic Insults

Murugeswari

Firoz

Subramani

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Murugeswari P, Firoz A, Murali S, et al. Vitamin-D3 (α-1, 25(OH) 2D3) protects retinal pigment epithelium from hyperoxic insults. Invest Ophthalmol Vis Sci. 2020;61(2):4. https://doi.org/10.1167/iovs.61.2.4 PURPOSE.Oxidative stress affects the retinal pigment epithelium (RPE) leading to development of vascular eye diseases. Cholecalciferol (VIT-D) is a known modulator of oxidative stress and angiogenesis. This in vitro study was carried out to evaluate the protective role of VIT-D on RPE cells incubated under hyperoxic conditions. METHODS.Cadaver primary RPE (PRPE) cells were cultured in hyperoxia (40% O 2 ) with or without VIT-D (α-1, 25(OH) 2D3). The functional and physiological effects of PRPE cells with VIT-D treatment were analyzed using molecular and biochemical tools. RESULTS.Vascular signaling modulators, such as vascular endothelial growth factor (VEGF) and Notch, were reduced in hyperoxic conditions but significantly upregulated in the presence of VIT-D. Additionally, PRPE conditioned medium with VIT-D induced the tubulogenesis in primary human umbilical vein endothelial cells (HUVEC) cells. VIT-D supplementation restored phagocytosis and transmembrane potential in PRPE cells cultured under hyperoxia. CONCLUSIONS. VIT-D protects RPE cells and promotes angiogenesis under hyperoxic insult.These findings may give impetus to the potential of VIT-D as a therapeutic agent in hyperoxia induced retinal vascular diseases.Keywords: retinal pigment epithelium, vitamin D, hyperoxia, vascular endothelial growth factor (VEGF), tubulogenesis O xidative stress is the result of an imbalance between the synthesis of reactive oxygen species (ROS) and the levels of antioxidants in the cells. It plays a major role in the pathophysiology of various ocular diseases, such as agerelated cataract, macular degeneration, glaucoma, diabetic retinopathy, and retinitis pigmentosa, by affecting cellular and vascular physiological aspects. 1,2 Antioxidants, such as enzymatic antioxidants, vitamins, minerals, carotenoids, and flavonoids, are the primary scavengers of ROS reducing levels of oxidative stress. 3 Cholecalciferol (vitamin-D3 (VIT-D)) has diverse functions, including modulation of inflammation, angiogenesis, oxidative stress, and fibrosis. 4,5 Recent studies have demonstrated an association between VIT-D and retinal pathophysiological conditions, such as age-related macular degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity (ROP). 6−8 These studies implicated deficiency of VIT-D to higher risk for early/late AMD, whereas a supplementation leads to delay or prevention in the progression of AMD. 6,9 Although VIT-D receptors as well as enzymes for VIT-D metabolism are present in the retina, choroid, and retinal pigment epithelium (RPE) cells, their functions are still not well understood. 6 VIT-D has been studied as a potential inhibitor of angiogenesis in a mouse model of oxygen-induced ischemic retinopathy (OIR). 10 A correlation of VIT-D and vascular endothelial growth factor (VEGF) has been ob...

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Section: Secreted Vegf Level Estimationmentioning

confidence: 99%

Vitamin-D3 (α-1, 25(OH) 2D3) Protects Retinal Pigment Epithelium From Hyperoxic Insults

Murugeswari

Firoz

Subramani

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…EGF and its receptors are commonly overexpressed in many solid tumors where it is associated with increased proliferation and tumor metastasis 36. Using a hydrogel in a microfluidic system, Truong et al demonstrated significantly increased breast cancer cell migration speed and persistence in response to a transient EGF gradient 37. In order to study the effects of spatially defined EGF gradients on breast cancer invasion, Fisher et al used two‐photon confocal microscopy to photopattern discrete EGF gradients within an HA‐based hydrogel and found increased invasion of MDA‐MB‐231 cells in the presence of EGF gradients ( Figure ) 38.…”

Section: Invasion Is Directed By the Physicochemical Environmentmentioning

confidence: 99%

“…The association of CAFs in tumor microenvironments with metastasis is well established; however, the dynamics of cell–cell communication leading to cell invasion is difficult to study in vivo. Using engineered hydrogel systems, researchers have been able to elucidate mechanisms of crosstalk between CAFs and cancer cells 37,51–55…”

Section: Coculture Effects On Cell Movement Through Hydrogelsmentioning

confidence: 99%

Designer Biomaterials to Model Cancer Cell Invasion In Vitro: Predictive Tools or Just Pretty Pictures?

Bahlmann

Smith

Shoichet

2020

Adv Funct Materials

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Metastasis is the leading cause of mortality in cancer patients. Underlying this process is the invasion and colonization of cancer cells into healthy tissues. Engineered hydrogel models of tumor microenvironments present an opportunity to understand the microenvironmental determinants of cellular invasion. The biochemical and mechanical cues, presented in the form of adhesion sites, degradable cues, matrix stiffness, and architecture, have significant effects on the extent of cancer cell migration, and the mechanisms employed by these cells to move through their matrix. Coculture with stromal cells such as cancer associated fibroblasts, endothelial cells, and immune cells that are associated with poor prognosis demonstrate that these cells exacerbate cancer cell invasion. With these models, researchers aim not only to recapitulate known cancer cell behaviors in a dish, but also to uncover new insights into mechanisms underlying these phenomena, paving the way for novel treatment strategies. In this perspective, the design of engineered models that are used to study cancer cell invasion and metastasis in vitro is discussed. To this end, the authors seek to understand and put into perspective: do these models reveal relevant mechanisms of cancer cell migration, or are they simply pretty pictures with little biological translatability?

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“…Experimental set ups span a range of complexities from simple hydrogel plugs in a multi-well plate (37) and filter insert (38), to more sophisticated 3 microfluidic platforms where different cell populations can be patterned into specific structures and tissue compartments. These microfluidic approaches have enabled real time monitoring of tumour cell invasion into neighbouring stromal tissue (39)(40)(41) and revealed dynamic events such as the transition to an invasive phenotype, colonization of adjacent compartments, and tumour cell extravasation. These changes in cell migration, morphology, and proliferation would be particularly challenging to quantify in animal or other in vitro culture models.…”

Section: Introductionmentioning

confidence: 99%

Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A Tissue Model to Probe Tumour Phenotypes at Tumour-Stroma Interfaces

D’Arcangelo

Chen

et al. 2019

Preprint

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The interface between a tumour and the adjacent stroma is a site of great importance for tumour development. At this site, carcinoma cells are highly proliferative, undergo invasive phenotypic changes, and directly interact with surrounding stromal cells, such as cancer-associated fibroblasts (CAFs) which further exert pro-tumorigenic effects. Here we describe the development of GLAnCE (Gels for Live Analysis of Compartmentalized Environments), an easy-to-use hydrogel-culture platform for investigating CAF-tumour cell interaction dynamics in vitro at a tumour-stroma interface. GLAnCE enables observation of CAF-mediated enhancement of both tumour cell proliferation and invasion at the tumour-stroma interface in real time, as well as stratification between phenotypes at the interface versus in the bulk tumour tissue compartment. We found that CAF presence resulted in the establishment of an invasionpermissive, interface-specific matrix environment, that leads to carcinoma cell movement outwards from the tumour edge and tumour cell invasion. Furthermore, the spatial stratification capability of GLAnCE was leveraged to discern differences between tumour cell epithelial-tomesenchymal (EMT) transition genes induced by paracrine signaling from CAFs versus genes induced by interface-specific, CAF-mediated microenvironment. GLAnCE combines high usability and tissue complexity, to provide a powerful in vitro platform to probe mechanisms of tumour cell movement specific to the microenvironment at the tumour-stroma interface.

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Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment

Cited by 116 publications

References 72 publications

Vitamin-D3 (α-1, 25(OH) 2D3) Protects Retinal Pigment Epithelium From Hyperoxic Insults

Vitamin-D3 (α-1, 25(OH) 2D3) Protects Retinal Pigment Epithelium From Hyperoxic Insults

Designer Biomaterials to Model Cancer Cell Invasion In Vitro: Predictive Tools or Just Pretty Pictures?

Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A Tissue Model to Probe Tumour Phenotypes at Tumour-Stroma Interfaces

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