Chemotherapeutic Stress Induces Transdifferentiation of Glioblastoma Cells to Endothelial Cells and Promotes Vascular Mimicry

Baisiwala, Shivani; Auffinger, Brenda; Caragher, Seamus P.; Shireman, Jack; Ahsan, Riasat; Lee, Gina; Hasan, Tanwir; Park, Cheol; Saathoff, Miranda; Christensen, Anne C.; Ahmed, Atique U.

doi:10.1155/2019/6107456

Cited by 34 publications

(53 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Information on clinical grade TMZ see package insert (URL: https://www.msd.de/fileadmin/ files/fachinformationen/temodal_hartkapseln.pdf, link accessed on 29 May 2020). Information on TMZ for animal experiments see [20,[41][42][43][44][45]. Table according to [31,[33][34][35]40,[46][47][48][49][50][51][52][53].…”

Section: Theophrastus Bombast Von Hohenheimmentioning

confidence: 99%

“…In contrast, during cell culture experiments TMZ is routinely dissolved in dimethyl sulfoxide (DMSO), an organic solvent commonly used in experimental settings for difficult to dissolve compounds, due to being miscible in water. Interestingly, for animal experiments it is frequently not stated which solvent was used to administer the drug, although DMSO [41,42], saline [20,43] and Ora-Plus [44,45] seem to be commonly used (see Figure 1). DMSO, however, is not an inert solvent.…”

Section: Eldridge Cleavermentioning

confidence: 99%

See 1 more Smart Citation

Considering the Experimental Use of Temozolomide in Glioblastoma Research

Herbener¹,

Burster

Goreth³

et al. 2020

Biomedicines

View full text Add to dashboard Cite

Temozolomide (TMZ) currently remains the only chemotherapeutic component in the approved treatment scheme for Glioblastoma (GB), the most common primary brain tumour with a dismal patient’s survival prognosis of only ~15 months. While frequently described as an alkylating agent that causes DNA damage and thus—ultimately—cell death, a recent debate has been initiated to re-evaluate the therapeutic role of TMZ in GB. Here, we discuss the experimental use of TMZ and highlight how it differs from its clinical role. Four areas could be identified in which the experimental data is particularly limited in its translational potential: 1. transferring clinical dosing and scheduling to an experimental system and vice versa; 2. the different use of (non-inert) solvent in clinic and laboratory; 3. the limitations of established GB cell lines which only poorly mimic GB tumours; and 4. the limitations of animal models lacking an immune response. Discussing these limitations in a broader biomedical context, we offer suggestions as to how to improve transferability of data. Finally, we highlight an underexplored function of TMZ in modulating the immune system, as an example of where the aforementioned limitations impede the progression of our knowledge.

show abstract

Section: Theophrastus Bombast Von Hohenheimmentioning

confidence: 99%

Section: Eldridge Cleavermentioning

confidence: 99%

Considering the Experimental Use of Temozolomide in Glioblastoma Research

Herbener¹,

Burster

Goreth³

et al. 2020

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Despite the usefulness and cytotoxicity of TMZ in glioblastoma cells, this molecule has also been associated with mechanisms that could favor tumor growth and relapse [ 195 ]. For example, a recent study indicated that chemotherapeutic stress induced by TMZ leads to trans-differentiation of glioblastoma cells to endothelial-like cells and promotes vasculogenic mimicry (VM) [ 196 ]. It is also important to mention that according to another study, although TMZ has a very good cytotoxic effect on the glioblastoma cells per se , it has almost no effect on glioblastoma-associated EC and is unable to reduce the peritumoral vascular density in vivo [ 197 ].…”

Section: Conventional and New Interventions That Target The Endothmentioning

confidence: 99%

Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies

Peleli

Moustakas

Papapetropoulos

2020

IJMS

View full text Add to dashboard Cite

Glioblastoma and other brain or CNS malignancies (like neuroblastoma and medulloblastoma) are difficult to treat and are characterized by excessive vascularization that favors further tumor growth. Since the mean overall survival of these types of diseases is low, the finding of new therapeutic approaches is imperative. In this review, we discuss the importance of the interaction between the endothelium and the tumor cells in brain and CNS malignancies. The different mechanisms of formation of new vessels that supply the tumor with nutrients are discussed. We also describe how the tumor cells (TC) alter the endothelial cell (EC) physiology in a way that favors tumorigenesis. In particular, mechanisms of EC–TC interaction are described such as (a) communication using secreted growth factors (i.e., VEGF, TGF-β), (b) intercellular communication through gap junctions (i.e., Cx43), and (c) indirect interaction via intermediate cell types (pericytes, astrocytes, neurons, and immune cells). At the signaling level, we outline the role of important mediators, like the gasotransmitter nitric oxide and different types of reactive oxygen species and the systems producing them. Finally, we briefly discuss the current antiangiogenic therapies used against brain and CNS tumors and the potential of new pharmacological interventions that target the EC–TC interaction.

show abstract

“…Other resistance molecular profiles conferring TMZ resistance to GBMs have also been reported, including overexpression of c-Met, P-glycoprotein, CD133, epidermal growth factor receptor, galectin-1, and Cdc20 proteins (10)(11)(12)(13). Several studies indicated that the mechanisms maintaining epithelialmesenchymal transition (EMT) and stem cell phenotype are also involved in TMZ resistance (14,15). However, few studies have explored TMZ response-related molecules at the gene transcription level, and no studies have investigated the clinical significance of gene expression signatures related to TMZ sensitivity in glioma.…”

Section: Introductionmentioning

confidence: 99%