3D breast cancer microtissue reveals the role of tumor microenvironment on the transport and efficacy of free-doxorubicin in vitro

Brancato, Virginia; Gioiella, Filomena; Imparato, Giorgia; Guarnieri, Daniela; Urciuolo, Francesco; Netti, Paolo A.

doi:10.1016/j.actbio.2018.05.055

Cited by 72 publications

(80 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the spheroid is reported to be an effective tool for the analysis of tumor activity and drug efficacy 42 , 43 , it has been reported that a the tight morphology of spheroids can hinder diffusion through a lack of extracellular matrix (ECM) compared to in vivo tissues 44 . Hence, the development of the ECM within HeLa/HUVEC spheroids was tested by immunostaining of E-cadherin marker (Supplemental Figure S2 ).…”

Section: Resultsmentioning

confidence: 99%

Generation of uniform-sized multicellular tumor spheroids using hydrogel microwells for advanced drug screening

Lee

Park

Yang

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Even though in vitro co-culture tumor spheroid model plays an important role in screening drug candidates, its wide applications are currently limited due to the lack of reliable and high throughput methods for generating well-defined and 3D complex co-culture structures. Herein, we report the development of a hydrogel microwell array to generate uniform-sized multicellular tumor spheroids. Our developed multicellular tumor spheroids are structurally well-defined, robust and can be easily transferred into the widely used 2D culture substrates while maintaining our designed multicellular 3D-sphere structures. Moreover, to develop effective anti-cancer therapeutics we integrated our recently developed gold-graphene hybrid nanomaterial (Au@GO)-based photothermal cancer therapy into a series of multicellular tumor spheroid co-culture system. The multicellular tumor spheroids were harvested onto a two-dimensional (2D) substrate, under preservation of their three-dimensional (3D) structure, to evaluate the photothermal therapy effectiveness of graphene oxide (GO)-wrapped gold nanoparticles (Au@GO). From the model of co-culture spheroids of HeLa/Ovarian cancer and HeLa/human umbilical vein endothelial cell (HUVEC), we observed that Au@GO nanoparticles displayed selectivity towards the fast-dividing HeLa cells, which could not be observed to this extent in 2D cultures. Overall, our developed uniform-sized 3D multicellular tumor spheroid could be a powerful tool for anticancer drug screening applications.

show abstract

Section: Resultsmentioning

confidence: 99%

Generation of uniform-sized multicellular tumor spheroids using hydrogel microwells for advanced drug screening

Lee

Park

Yang

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…This is because, while in the 3D‐μTP model DOX was able to penetrate the bead and act on all cells, in the spheroid model, the tight cell–cell adhesion, driven by E‐cadherin, at spheroid surface prevented DOX penetration. Additionally, a protective effect from fibroblasts decreased chemosensitivity in both coculture models (Brancato et al, 2018). In sum, the multicellular spheroid model provides significant advantages for drug testing and studying mechanisms of drug resistance, like 3D transport gradients and CAM‐DR, over the traditional 2D TCPS.…”

Section: Multicellular Spheroid Modelsmentioning

confidence: 99%

“…ATPS study revealed that the signaling between the CXCL12 cytokine secreted by CAFs and the associated receptor CXCR‐4 activated the MAPK/PI3K pathway driving proliferation and drug resistance (Ham et al, 2018). In another coculture study, Brancato et al (2018) compared the applicability of the basic spheroid model to a 3D microtissue (3D‐μTP) scaffold in which the cells spread throughout a porous gelatin microbead to test the efficacy of DOX on MCF7 breast cancer cells with and without incorporation of CAFs (Brancato et al, 2018). The aim of the 3D‐μTP was to effectively recreate endogenous ECM and investigate its effect on drug‐uptake.…”

Section: Multicellular Spheroid Modelsmentioning

confidence: 99%

Three‐dimensional culture models to study drug resistance in breast cancer

Fisher

Rao

2020

Biotech & Bioengineering

View full text Add to dashboard Cite

Despite recent advances in breast cancer treatment, drug resistance frequently presents as a challenge, contributing to a higher risk of relapse and decreased overall survival rate. It is now generally recognized that the extracellular matrix and cellular heterogeneity of the tumor microenvironment influences the cancer cells' ultimate fate. Therefore, strategies employed to examine mechanisms of drug resistance must take microenvironmental influences, as well as genetic mutations, into account. This review discusses three‐dimensional (3D) in vitro model systems which incorporate microenvironmental influences to study mechanisms of drug resistance in breast cancer. These bioengineered models include spheroid‐based models, biomaterial‐based models such as polymeric scaffolds and hydrogels, and microfluidic chip‐based models. The advantages of these model systems over traditionally studied two‐dimensional tissue culture polystyrene are examined. Additionally, the applicability of such 3D models for studying the impact of tumor microenvironment signals on drug response and/or resistance is discussed. Finally, the potential of such models for use in the development of strategies to combat drug resistance and determine the most promising treatment regimen is explored.

show abstract

“…The diffusion coefficient of anticancer drugs and the drug action for the 3D MCF-7-CAF microtissues with GPM were higher than those for the GPM-free 3D MCF-7-CAF. In addition, there was a good correlation of the expression of some cancer biomarkers related to cell junctions between the 3D MCF-7-CAF microtissues combined with GPM and in vivo cancer site [ 98 ]. The combination of endothelial cells with the culture system is reported [ 66 ].…”

Section: 3d Coculture System Of Cancer and Stromal Cells Combined mentioning

confidence: 99%

Three-Dimensional Culture System of Cancer Cells Combined with Biomaterials for Drug Screening

Nii

Makino

Tabata

2020

Cancers

118

117

View full text Add to dashboard Cite

Anticancer drug screening is one of the most important research and development processes to develop new drugs for cancer treatment. However, there is a problem resulting in gaps between the in vitro drug screening and preclinical or clinical study. This is mainly because the condition of cancer cell culture is quite different from that in vivo. As a trial to mimic the in vivo cancer environment, there has been some research on a three-dimensional (3D) culture system by making use of biomaterials. The 3D culture technologies enable us to give cancer cells an in vitro environment close to the in vivo condition. Cancer cells modified to replicate the in vivo cancer environment will promote the biological research or drug discovery of cancers. This review introduces the in vitro research of 3D cell culture systems with biomaterials in addition to a brief summary of the cancer environment.

show abstract

3D breast cancer microtissue reveals the role of tumor microenvironment on the transport and efficacy of free-doxorubicin in vitro

Cited by 72 publications

References 53 publications

Generation of uniform-sized multicellular tumor spheroids using hydrogel microwells for advanced drug screening

Generation of uniform-sized multicellular tumor spheroids using hydrogel microwells for advanced drug screening

Three‐dimensional culture models to study drug resistance in breast cancer

Three-Dimensional Culture System of Cancer Cells Combined with Biomaterials for Drug Screening

Contact Info

Product

Resources

About