Microenvironmental Regulation of Tumor Angiogenesis: Biological and Engineering Considerations

Infanger, David W.; Pathi, Siddharth P.; Fischbach, Claudia

doi:10.1007/978-1-4419-7835-6_8

Cited by 2 publications

(2 citation statements)

References 195 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among various 3D models, tumor aggregates, often referred to as spheroids or microtumors, are multicellular structures that have been widely used to study (1) cell-cell interactions, 7,8 (2) microenvironmental cues important for tumor growth, 5 (3) to understand complex phenomena such as angiogenesis, [9][10][11][12][13][14] and (4) to test drug penetration, tumor responses, and drug resistance. 15,16 Microtumors have been shown to recapitulate various aspects of solid tumors in vivo, including their responses to cancer drugs (e.g., development of multidrug resistance), and can serve as good models for preclinical drug testing.…”

mentioning

confidence: 99%

Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation

Singh

Mukundan

et al. 2015

ASSAY and Drug Development Technologies

View full text Add to dashboard Cite

Despite significant investments in cancer research and drug discovery/development, the rate of new cancer drug approval is £5% and most cases of metastatic cancer remain incurable. Ninety-five percent of new cancer drugs fail in clinical development because of a lack of therapeutic efficacy and/or unacceptable toxicity. One of the major factors responsible for the low success rate of anticancer drug development is the failure of preclinical models to adequately recapitulate the complexity and heterogeneity of human cancer. For throughput and capacity reasons, high-throughput screening growth inhibition assays almost exclusively use two-dimensional (2D) monolayers of tumor cell lines cultured on tissue culture-treated plastic/glass surfaces in serum-containing medium. However, these 2D tumor cell line cultures fail to recapitulate the three-dimensional (3D) context of cells in solid tumors even though the tumor microenvironment has been shown to have a profound effect on anticancer drug responses. Tumor spheroids remain the best characterized and most widely used 3D models; however, spheroid sizes tend to be nonuniform, making them unsuitable for high-throughput drug testing. To circumvent this challenge, we have developed defined size microwell arrays using nonadhesive hydrogels that are applicable to a wide variety of cancer cell lines to fabricate sizecontrolled 3D microtumors. We demonstrate that the hydrogel microwell array platform can be applied successfully to generate hundreds of uniform microtumors within 3-6 days from many cervical and breast, as well as head and neck squamous cell carcinoma (HNSCC) cells. Moreover, controlling size of the microwells in the hydrogel array allows precise control over the size of the microtumors. Finally, we demonstrate the application of this platform technology to probe activation as well as inhibition of epidermal growth factor receptor (EGFR) signaling in 3D HNSCC microtumors in response to EGF and cetuximab treatments, respectively. We believe that the ability to generate large numbers of HNSCC microtumors of uniform size and 3D morphology using hydrogel arrays will provide more physiological in vitro 3D tumor models to investigate how tumor size influences signaling pathway activation and cancer drug efficacy.

show abstract

mentioning

confidence: 99%

Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation

Singh

Mukundan

et al. 2015

ASSAY and Drug Development Technologies

View full text Add to dashboard Cite

show abstract

“…For example, tumors in a murine xenograft model grow relatively faster than human tumors, which results in immature blood vessels that cannot compare with tumorigenic vessels that have been established for a longer period of time [16, 17]. In addition, key parameters that affect tumor progression, including oxygen tension, nutrient gradients, and mechanical forces, cannot be easily controlled and manipulated in these models [9]. Imaging tumor vasculature in vivo has been particularly challenging as well, making it difficult to evaluate the benefits from anti-angiogenic therapies [15, 18].…”

Section: Introductionmentioning

confidence: 99%

Hydrogels to model 3D in vitro microenvironment of tumor vascularization

Song¹,

Park²,

Gerecht³

2014

Advanced Drug Delivery Reviews

139

111

View full text Add to dashboard Cite

A growing number of failing clinical trials for cancer therapy is substantiating the need to upgrade the current practice in culturing tumor cells and modeling tumor angiogenesis in vitro. Many attempts have been made to engineer vasculature in vitro by utilizing hydrogels, but the application of these tools in simulating in vivo tumor angiogenesis is still very new. In this review, we explore current use of hydrogels and their design parameters to engineer vasculogenesis and angiogenesis and to evaluate the angiogenic capability of cancerous cells and tissues. When coupled with other technologies such as lithography and three-dimensional printing, one can even create an advanced microvessel model as microfluidic channels to more accurately capture the native angiogenesis process.

show abstract

Microenvironmental Regulation of Tumor Angiogenesis: Biological and Engineering Considerations

Cited by 2 publications

References 195 publications

Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation

Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation

Hydrogels to model 3D in vitro microenvironment of tumor vascularization

Contact Info

Product

Resources

About