Gather Round: In vitro tumor spheroids as improved models of in vivo tumors

Chandrasekaran, Siddarth

doi:10.4172/2155-9538.1000e109

Cited by 16 publications

(14 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, MCT4 induction, associated with activated stromal recruitment by breast cancer cells, can be blocked by antioxidants such as N-acetyl-cysteine, quercetin and metformin, as . Abnormal tumor microenvironment results from structural parameters generated in the process of solid tumor formation [Chandrasekaran and King, 2012].ATP, adenosine triphosphate.…”

Section: Oxidative Stress/inflammation: Primary Role In Disease Progrmentioning

confidence: 99%

See 1 more Smart Citation

Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic approach to disease progression and recurrence

Crawford

2014

Ther Adv Med Oncol

View full text Add to dashboard Cite

Abstract:The chronic, progressive clinical characteristics of many adult solid tumor malignancies suggest that a more effective therapeutic approach to cancer management may require long-term intervention using nontoxic systemic agents that block critical components of abnormal tumor physiology. Two highly promising systemic targets common to the development, progression and recurrence of many common cancers are dysregulated inflammatory and oxidation/reduction (redox) pathways. Compelling clinical data support the use of anti-inflammatory and antioxidant agents as a therapeutic modality for long-term use in patients diagnosed with several common cancers, including colon cancer and breast cancer. The therapeutic paradigm presented in this paper is the product of a synthesis of what is currently understood about the biological effects of inflammation and oxidative stress that contribute to tumorigenesis, disease progression and recurrence as well as results obtained from research on the use of prophylactics with anti-inflammatory or antioxidant properties in cancer prevention and treatment.

show abstract

Section: Oxidative Stress/inflammation: Primary Role In Disease Progrmentioning

confidence: 99%

“…Abnormal tumor microenvironment results from structural parameters generated in the process of solid tumor formation [Chandrasekaran and King, 2012]. ATP, adenosine triphosphate.…”

Section: Three-dimensional Tumor Structure: Biophysical Link To Oxidamentioning

confidence: 99%

Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic approach to disease progression and recurrence

Crawford

2014

Ther Adv Med Oncol

View full text Add to dashboard Cite

show abstract

“…Additionally, they can resemble the clinical situation even more by including multiple cell types that are typically found in the tumor microenvironment, such as tumor-associated fibroblasts and immune cells 5,8,[32][33][34] . The 3D micro-environment in such cultures resembles clinical avascular tumor nodules, as an extracellular matrix is formed that may act as a major physical barrier for drug penetration 31 .…”

Section: Graphical Abstract Introductionmentioning

confidence: 99%

Sonoprinting liposomes on tumor spheroids by microbubbles and ultrasound

Roovers

Deprez

Priwitaningrum

et al. 2019

Journal of Controlled Release

View full text Add to dashboard Cite

Ultrasound-triggered drug-loaded microbubbles have great potential for drug delivery due to their ability to locally release drugs and simultaneously enhance their delivery into the target tissue. We have recently shown that upon applying ultrasound, nanoparticle-loaded microbubbles can deposit nanoparticles onto cells grown in 2D monolayers, through a process that we termed "sonoprinting". However, the rigid surfaces on which cell monolayers are typically growing might be a source of acoustic reflections and aspherical microbubble oscillations, which can influence microbubble-cell interactions. In the present study, we aim to reveal whether sonoprinting can also occur in more complex and physiologically relevant tissues, by using free-floating 3D tumor spheroids as a tissue model. We show that both monospheroids (consisting of tumor cells alone) and cospheroids (consisting of tumor cells and fibroblasts, which produce an extracellular matrix) can be sonoprinted. Using doxorubicin-liposome-loaded microbubbles, we show that sonoprinting allows to deposit large amounts of doxorubicin-containing liposomes to the outer cell layers of the spheroids, followed by doxorubicin release into the deeper layers of the spheroids, resulting in a significant reduction in cell viability. Sonoprinting may become an attractive approach to deposit drug patches at the surface of tissues, thereby promoting the delivery of drugs into target tissues.

show abstract

“…Cell-cell interactions in primary tumors have been shown to play a significant role in determining the fate of a cell that leaves the primary site and enters the peripheral circulation [15] . Though cancer cell lines serve as a good model for studying different aspects of the metastatic cascade, physiologically relevant interactions may be lost in 2D monolayer culture [16] . The dimensionality of the system used to study cancer has an important role in studying several aspects of cancer biology.…”

Section: Introductionmentioning

confidence: 99%

TRAIL-Mediated Apoptosis in Breast Cancer Cells Cultured as 3D Spheroids

et al. 2014

Self Cite

View full text Add to dashboard Cite

TNF-alpha-related-apoptosis-inducing-ligand (TRAIL) has been explored as a therapeutic drug to kill cancer cells. Cancer cells in the circulation are subjected to apoptosis-inducing factors. Despite the presence of these factors, cells are able to extravasate and metastasize. The homotypic and heterotypic cell-cell interactions in a tumor are known to play a crucial role in bestowing important characteristics to cancer cells that leave the primary site. Spheroid cell culture has been extensively used to mimic these physiologically relevant interactions. In this work, we show that the breast cancer cell lines BT20 and MCF7, cultured as 3D tumor spheroids, are more resistant to TRAIL-mediated apoptosis by downregulating the expression of death receptors (DR4 and DR5) that initiate TRAIL-mediated apoptosis. For comparison, we also investigated the effect of TRAIL on cells cultured as a 2D monolayer. Our results indicate that tumor spheroids are enriched for CD44hiCD24loALDH1hi cells, a phenotype that is predominantly known to be a marker for breast cancer stem cells. Furthermore, we attribute the TRAIL-resistance and cancer stem cell phenotype observed in tumor spheroids to the upregulation of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway. We show that inhibition of the COX-2/PGE2 pathway by treating tumor spheroids with NS-398, a selective COX-2 inhibitor, reverses the TRAIL-resistance and decreases the incidence of a CD44hiCD24lo population. Additionally, we show that siRNA mediated knockdown of COX-2 expression in MCF7 cells render them sensitive to TRAIL by increasing the expression of DR4 and DR5. Collectively, our results show the effect of the third-dimension on the response of breast cancer cells to TRAIL and suggest a therapeutic target to overcome TRAIL-resistance.

show abstract

Gather Round: In vitro tumor spheroids as improved models of in vivo tumors

Cited by 16 publications

References 16 publications

Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic approach to disease progression and recurrence

Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic approach to disease progression and recurrence

Sonoprinting liposomes on tumor spheroids by microbubbles and ultrasound

TRAIL-Mediated Apoptosis in Breast Cancer Cells Cultured as 3D Spheroids

Contact Info

Product

Resources

About