Ultrastructural study of osteosarcomas

Garbe, L; Monges, G; Pellegrin, E; Payan, H.L.

doi:10.1016/s0046-8177(81)80193-1

Cited by 12 publications

(4 citation statements)

References 8 publications

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“…The most prominent was interdigitation of adjacent cells often punctuated by desmosomes [9]. EM of osteosarcoma component revealed matrix with scattered collagen fibers and focal calcium deposits [10]. …”

Section: Resultsmentioning

confidence: 99%

Post-radiation dedifferentiation of meningioma into osteosarcoma.

Osipov

Krouwer

et al. 2002

BMC Cancer

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Section: Resultsmentioning

confidence: 99%

Post-radiation dedifferentiation of meningioma into osteosarcoma.

Osipov

Krouwer

et al. 2002

BMC Cancer

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“…According to literature, both variants have been described. Ultrastructural analysis of osteosarcoma cell described lipid droplets in all types of osteosarcoma cells [42]. Osteoblasts can trans-differentiate to [43,44].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of osteosarcoma identifies suppression of wnt pathway and up-regulation of adiponectin as potential biomarker

Märtson¹,

Kõks²,

Reimann³

et al. 2013

Genomics Discov

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Osteosarcoma (OS) is primary malignant bone tumour with complicated early diagnosis. There are no specific markers currently available for predicting the prognosis and chemosensitivity of OS. In present study we performed transcriptome profiling of single patient tumour tissue with RNA-seq technology. We analysed surgically removed sarcoma sample from single 16 years old male patient. Transciptome analysis was done with RNA-seq technology, bioinformatics with Lifescope and R Bioconductor. Validation experiments were done with quantitative real-time PCR (QRTPCR). After quality and coverage filtering, RNA-seq experiment resulted 29,311,899 mapped reads for sarcoma and 22,099,159 mapped reads for normal bone tissue. 65 genes were differentially expressed with FDR corrected statistical significance below 0.05. Seven genes were down-regulated and 58 genes were up-regulated in sarcoma. The most highly up-regulated gene in sarcoma was adiponectin, ADIPOQ (with adjusted p-value 5.5E-07, log2 fold change was 7.9). Many of the genes we found are related to the adipose tissue metabolism (ADIPOQ, PLIN1, FABP4) and to the Wnt signalling suppression (WIF1, SOST). We also found novel fusion transcript between the genes LMTK2 and ZSWIM5. LMTK2 is lemur tyrosine kinase 2, and it has been shown to be involved in NGF-TrkA signalling. Interestingly, studies support the involvement of LMTK2 in development of prostate cancer. ZSWIM5 is zinc finger SWIM domain protein 5 and its function is not known. Immunohistochemical analysis confirmed positive staining for adiponectin in osteosarcoma. This paper is a good illustration how transcriptome analysis can find new biomarkers and targets for complex diseases.

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“…However, since the metabolomics experiments in the current study were conducted using A498 cells only, it may not be possible to extrapolate to other cc-RCC cells in regards to the disruption of lipid metabolism by englerin A culminating in ER stress and cell death. Notably, according to the results of cytotoxicity profiling of englerin A in over 500 cancer cell lines, [21] the cancer cell types most sensitive to englerin A, in addition to renal cancer cells, included those of bone, central nervous system, and liver, all of which are known to store relatively large amounts of lipids [55–59]. This finding is in line with our results and further supports lipid metabolism and ER stress as a targetable vulnerability in lipid storing tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Englerin A induces an acute inflammatory response and reveals lipid metabolism and ER stress as targetable vulnerabilities in renal cell carcinoma

et al. 2017

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Renal cell carcinoma (RCC) is among the top ten most common forms of cancer and is the most common malignancy of the kidney. Clear cell renal carcinoma (cc-RCC), the most common type of RCC, is one of the most refractory cancers with an incidence that is on the rise. Screening of plant extracts in search of new anti-cancer agents resulted in the discovery of englerin A, a guaiane sesquiterpene with potent cytotoxicity against renal cancer cells and a small subset of other cancer cells. Though a few cellular targets have been identified for englerin A, it is still not clear what mechanisms account for the cytotoxicity of englerin A in RCC, which occurs at concentrations well below those used to engage the targets previously identified. Unlike any prior study, the current study used a systems biology approach to explore the mechanism(s) of action of englerin A. Metabolomics analyses indicated that englerin A profoundly altered lipid metabolism by 24 h in cc-RCC cell lines and generated significant levels of ceramides that were highly toxic to these cells. Microarray analyses determined that englerin A induced ER stress signaling and an acute inflammatory response, which was confirmed by quantitative PCR and Western Blot analyses. Additionally, fluorescence confocal microscopy revealed that englerin A at 25 nM disrupted the morphology of the ER confirming the deleterious effect of englerin A on the ER. Collectively, our findings suggest that cc-RCC is highly sensitive to disruptions in lipid metabolism and ER stress and that these vulnerabilities can be targeted for the treatment of cc-RCC and possibly other lipid storing cancers. Furthermore, our results suggest that ceramides may be a mediator of some of the actions of englerin A. Lastly, the acute inflammatory response induced by englerin A may mediate anti-tumor immunity.

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Ultrastructural study of osteosarcomas

Cited by 12 publications

References 8 publications

Post-radiation dedifferentiation of meningioma into osteosarcoma.

Post-radiation dedifferentiation of meningioma into osteosarcoma.

Transcriptome analysis of osteosarcoma identifies suppression of wnt pathway and up-regulation of adiponectin as potential biomarker

Englerin A induces an acute inflammatory response and reveals lipid metabolism and ER stress as targetable vulnerabilities in renal cell carcinoma

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