Tumor-on-a-chip for integrating a 3D tumor microenvironment: chemical and mechanical factors

Wan, Li; Neumann, Carola A.; LeDuc, Philip R.

doi:10.1039/c9lc00550a

Cited by 84 publications

(67 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypoxia typically develops once the tumors grow beyond 1 cm 35 , 36 . Furthermore, hypoxia is also one of the factors that accelerate the production of ATP, which is rapidly converted to adenosine resulting in an anti-inflammatory response 7 , 8 , 37 . Our results demonstrated, that the inhibitory effects of the lack of CD73 on cell viability were hypoxia-dependent.…”

Section: Discussionmentioning

confidence: 99%

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

Petruk

Tuominen

Åkerfelt

et al. 2021

Sci Rep

View full text Add to dashboard Cite

CD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition.

show abstract

Section: Discussionmentioning

confidence: 99%

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

Petruk

Tuominen

Åkerfelt

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…High-throughput screening approaches that also try to identify the influence of various compositional parameters (e.g., charge ratio and membrane charge density) on the transfection efficiency in ever more realistic in vitro models (including the influence of serum and protein absorption) may reveal unexpected behavior to be explored for improved therapeutic outcomes. This task may be facilitated by new in vitro tumor-on-a-chip platforms that allow mimicking several important aspects of the tumor microenvironment, and can be used for high-throughput screening of new anticancer formulations [226,227]. Simultaneously, new microfluidic methods are also now in use that allow the preparation of lipid-NA NPs in a more rapid, controlled and reproducible away, promising to optimize the assembly of these particles even further and accelerate the discovery of more potent formulations [175,180,[183][184][185][228][229][230].…”

Section: Prospectsmentioning

confidence: 99%

Lipid-Nucleic Acid Complexes: Physicochemical Aspects and Prospects for Cancer Treatment

2020

View full text Add to dashboard Cite

Cancer is an extremely complex disease, typically caused by mutations in cancer-critical genes. By delivering therapeutic nucleic acids (NAs) to patients, gene therapy offers the possibility to supplement, repair or silence such faulty genes or to stimulate their immune system to fight the disease. While the challenges of gene therapy for cancer are significant, the latter approach (a type of immunotherapy) starts showing promising results in early-stage clinical trials. One important advantage of NA-based cancer therapies over synthetic drugs and protein treatments is the prospect of a more universal approach to designing therapies. Designing NAs with different sequences, for different targets, can be achieved by using the same technologies. This versatility and scalability of NA drug design and production on demand open the way for more efficient, affordable and personalized cancer treatments in the future. However, the delivery of exogenous therapeutic NAs into the patients’ targeted cells is also challenging. Membrane-type lipids exhibiting permanent or transient cationic character have been shown to associate with NAs (anionic), forming nanosized lipid-NA complexes. These complexes form a wide variety of nanostructures, depending on the global formulation composition and properties of the lipids and NAs. Importantly, these different lipid-NA nanostructures interact with cells via different mechanisms and their therapeutic potential can be optimized to promising levels in vitro. The complexes are also highly customizable in terms of surface charge and functionalization to allow a wide range of targeting and smart-release properties. Most importantly, these synthetic particles offer possibilities for scaling-up and affordability for the population at large. Hence, the versatility and scalability of these particles seem ideal to accommodate the versatility that NA therapies offer. While in vivo efficiency of lipid-NA complexes is still poor in most cases, the advances achieved in the last three decades are significant and very recently a lipid-based gene therapy medicine was approved for the first time (for treatment of hereditary transthyretin amyloidosis). Although the path to achieve efficient NA-delivery in cancer therapy is still long and tenuous, these advances set a new hope for more treatments in the future. In this review, we attempt to cover the most important biophysical and physicochemical aspects of non-viral lipid-based gene therapy formulations, with a perspective on future cancer treatments in mind.

show abstract

“…[ 110,111 ] Also, they can provide the establishment of physical/chemical gradients in the device, such as hypoxia, molecules concentration gradients, or shear stress, an approach that can be used to study how these conditions affect the tumor progression or chemotherapeutics resistance. [ 112 ] They also allow the study of the effect produced by specific therapeutics, nanoparticles (NPs) or cells, angiogenesis, [ 113,114 ] or to study cancer cells extravasation or micrometastasis, [ 115 ] making them very suitable for fundamental studies. These devices are generally fabricated with polydimethylsiloxane or thermoplastics through photolithography, and hydrogels can be introduced inside the chips for culturing cells in a 3D setting and under dynamic flow conditions.…”

Section: Hydrogels and The Tumor Microenvironment Ecmmentioning

confidence: 99%

Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models

et al. 2021

View full text Add to dashboard Cite

The establishment of tumor microenvironment using biomimetic in vitro models that recapitulate key tumor hallmarks including the tumor supporting extracellular matrix (ECM) is in high demand for accelerating the discovery and preclinical validation of more effective anticancer therapeutics. To date, ECM‐mimetic hydrogels have been widely explored for 3D in vitro disease modeling owing to their bioactive properties that can be further adapted to the biochemical and biophysical properties of native tumors. Gathering on this momentum, herein the current landscape of intrinsically bioactive protein and peptide hydrogels that have been employed for 3D tumor modeling are discussed. Initially, the importance of recreating such microenvironment and the main considerations for generating ECM‐mimetic 3D hydrogel in vitro tumor models are showcased. A comprehensive discussion focusing protein, peptide, or hybrid ECM‐mimetic platforms employed for modeling cancer cells/stroma cross‐talk and for the preclinical evaluation of candidate anticancer therapies is also provided. Further development of tumor‐tunable, proteinaceous or peptide 3D microtesting platforms with microenvironment‐specific biophysical and biomolecular cues will contribute to better mimic the in vivo scenario, and improve the predictability of preclinical screening of generalized or personalized therapeutics.

show abstract

Tumor-on-a-chip for integrating a 3D tumor microenvironment: chemical and mechanical factors

Abstract: Tumor progression is significantly influenced by factors such as mechanical force, shear stress, chemotaxis, and hypoxia. Here, we reviewed recent achievements and presented potential directions for tumor-on-a-chip systems in the future.

Cited by 84 publications

References 128 publications

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

Lipid-Nucleic Acid Complexes: Physicochemical Aspects and Prospects for Cancer Treatment

Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models

Contact Info

Product

Resources

About