Understanding Micrometastatic Disease and <i>Anoikis</i> Resistance in Ewing Family of Tumors and Osteosarcoma

Strauss, Sandra J.; Ng, Tony; Mendoza-Naranjo, Ariadna; Whelan, Jeremy; Sorensen, Poul H.

doi:10.1634/theoncologist.2010-0093

Cited by 50 publications

(42 citation statements)

References 85 publications

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“…As a barrier to metastasis, cells normally undergo an apoptotic process known as “anoikis”, a form of cell death due to loss of contact with the extracellular matrix [4–6]. Cancer cells acquire anoikis resistance to survive after detachment from primary sites and travel through the circulatory and lymphatic systems to disseminate throughout the body [7].…”

Section: Introductionmentioning

confidence: 99%

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells

Lee

et al. 2017

PLoS ONE

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Background & aimsAcquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells.MethodsWe compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial–mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model.ResultsAR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib.ConclusionsThese results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC.

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Section: Introductionmentioning

confidence: 99%

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells

Lee

et al. 2017

PLoS ONE

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“…Cadherin is a type of cell surface protein, which regulates isoantigens and calcium-dependent cellcell adhesion (Asiaf et al, 2014); it has been shown to be very important for cellular structure and differentiation (Frisch and Screaton, 2001;Marco et al, 2003). Studies have shown that the E-cadherin signaling pathway can inhibit anoikis avoidance in Ewing's sarcoma (Kang et al, 2007;Strauss et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Correlation between E-Cadherin-Regulated Cell Adhesion and Human Osteosarcoma MG-63 Cell Anoikis

Lin

Cai²,

Ding³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Purpose: The aim of this study was to investigate the relationship between cell adhesion and anoikis evasion among human osteosarcoma cells (MG-63), and to further study the molecular mechanisms. Materials and Methods: Human osteosarcoma cells (MG-63) were assessed for apoptosis, and caspase-3, E-cadherin and β-catenin expression in EDTA and control non-EDTA groups. Results: MG-63 cells were predominantly aggregated when in suspension, and the suspended cells were more dispersed in the EDTA group. Following culture in suspension for 24 h, 48 h, or 72 h, the rates of apoptosis were 34.88%±3.64%, 59.3%±7.22% and 78.5%±5.21% in the experimental group and 7.34%±2.13%, 14.7%±3.69%, and 21.4%±3.60% in the control group, respectively. Caspase-3 expression progressively increased and E-cadherin and β-catenin were decreased in the experimental group, whereas there was no change in the control group. Conclusions: MG-63 cells could avoid anoikis through cell adhesion, and E-cadherin might play a role in this process.

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“…As such, ES spheroids have been used extensively to judge the effectiveness of chemotherapeutic and biologically targeted drugs (Figure 3) [53, 67, 80, 86, 87], to study the impact of cell signaling pathways that regulate ES cell proliferation [53, 80, 88], to investigate the effects of tumor architecture upon immune cell function, and to identify suitable antigens for immunotherapeutic strategies [89, 90]. ES MCTS have also proven useful for modeling micrometastatic disease, contributed to our understanding of anoikis (a form of cell death that results from lost ECM contact) [53, 88], and served as a platform to evaluate heterotypic interactions between tumor cells and vascular progenitor cells responsible for angiogenesis [77].…”

Section: Tumor Structures and Ecm Generation Intrinsic To The Cancmentioning

confidence: 99%

3D tissue-engineered model of Ewing's sarcoma

Lamhamedi-Cherradi

Santoro

Ramammoorthy

et al. 2014

Advanced Drug Delivery Reviews

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Despite longstanding reliance upon monolayer culture for studying cancer cells, and numerous advantages from both a practical and experimental standpoint, a growing body of evidence suggests more complex three-dimensional (3D) models are necessary to properly mimic many of the critical hallmarks associated with the oncogenesis, maintenance and spread of Ewing sarcoma (ES), the second most common pediatric bone tumor. And as clinicians increasingly turn to biologically-targeted therapies that exert their effects not only on the tumor cells themselves, but also on the surrounding extracellular matrix, it is especially important that preclinical models evolve in parallel to reliably measure antineoplastic effects and possible mechanisms of de novo and acquired drug resistance. Herein, we highlight a number of innovative methods used to fabricate biomimetic ES tumors, encompassing both the surrounding cellular milieu and extracellular matrix (ECM), and suggest potential applications to advance our understanding of ES biology, preclinical drug testing, and personalized medicine.

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Understanding Micrometastatic Disease and Anoikis Resistance in Ewing Family of Tumors and Osteosarcoma

Cited by 50 publications

References 85 publications

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells

Correlation between E-Cadherin-Regulated Cell Adhesion and Human Osteosarcoma MG-63 Cell Anoikis

3D tissue-engineered model of Ewing's sarcoma

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