Differential expression of angiogenesis markers HSP70, HSP90, VEGF and pERK1/2 in both components of dedifferentiated chondrosarcomas

Schoedel, Karen E.; Miller, Virginia; Osei-Hwedieh, David O.; Watters, Rebecca; Duensing, Anette; John, Ivy; Chandran, Uma; Chang, Alexander R.; Soman, Vishal; Weiß, Kurt

doi:10.1016/j.jbo.2021.100370

Cited by 3 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study showed that L-2-HG, another enantiomer of 2-HG, is increased in hypoxia, leading to the increased methylation of histone repressive marks such as H3K9me3 (43,44). Furthermore, a recent study showed increased expression of the HSPs HSP and HSP in DDCS (45), corroborating the findings of upregulation of HIF2α in CS progression (46).…”

Section: Discussionmentioning

confidence: 68%

Distinct IDH1/2-associated Methylation Profile and Enrichment ofTP53andTERTMutations Distinguish Dedifferentiated Chondrosarcoma from Conventional Chondrosarcoma

Dermawan

Nafa

Mohanty

et al. 2023

Cancer Research Communications

View full text Add to dashboard Cite

Dedifferentiated chondrosarcoma (DDCS) is a rare high-grade chondrosarcoma characterized by a well-differentiated chondrosarcoma (WDCS) component that abruptly transitions to a high-grade, non-cartilaginous sarcomatous component. To date, the molecular pathogenesis of DDCS and its distinction from conventional chondrosarcoma remain poorly understood. By targeted sequencing, we examined the mutational and copy number profiles of 18 DDCS, including macrodissected WDCS components, compared to 55 clinically sequenced conventional chondrosarcomas. In conjunction with publicly available external data, we analyzed the methylation and expression profiles of 34 DDCS and 94 conventional chondrosarcomas. IDH1/IDH2 mutations were present in 36% conventional chondrosarcomas and 71% DDCS. Compared to conventional chondrosarcomas, DDCS had higher frequencies of TP53 and TERT promoter mutations and CDKN2A/B copy number losses. Paired analysis of macrodissected WDCS and the high-grade components revealed TERT promoter mutations as early events. Despite phenotypic similarities, the percentage of genome with copy number alterations in DDCS was significantly lower than that in other high-grade sarcomas. Differential methylation analysis revealed reduction of IDH1/IDH2-associated global hypermethylation characteristically seen in conventional chondrosarcoma and a distinct methylation profile in DDCS. The WDCS and high-grade components in DDCS showed similar methylation profiles. These CpG sites were associated with upregulated expression of genes involved in G2M checkpoints and E2F targets. Genomic profiling revealed enrichment of TP53, TERT promoter and CDKN2A/B alterations in DDCS. Integrated methylation and gene expression analysis revealed distinct IDH1/IDH2-associated methylation and transcriptional profiles as early events in DDCS, which may underly the pathogenesis of dedifferentiation in chondrosarcomas.

show abstract

Section: Discussionmentioning

confidence: 68%

Distinct IDH1/2-associated Methylation Profile and Enrichment ofTP53andTERTMutations Distinguish Dedifferentiated Chondrosarcoma from Conventional Chondrosarcoma

Dermawan

Nafa

Mohanty

et al. 2023

Cancer Research Communications

View full text Add to dashboard Cite

show abstract

“…The observed presence of HSP70 in the nuclei of epithelial cells during the follicular and luteal phases is difficult to interpret, although a selective transfer of HSP70 from the cytoplasm to the nucleus has been detected (Mehlen and Arrigo 1994 ). It has been reported that the nuclear localization of HSP70 has a role in inhibiting apoptosis (Schoedel et al 2021 ) and in the heat shock response in vitiligo (Abdou et al 2013 ). Long-term exposure of bovine oviduct epithelial cells to high temperature (41 °C) increased the expression of HSP70 with no effect on cell viability, suggesting its putative protective role (Rapala et al 2018 ).…”

Section: Discussionmentioning

confidence: 99%

The abundance and localization of heat shock proteins (HSP)-60, -70, and -90 in the oviductal ampulla of hamadryas baboon (Papio hamadryas) during the menstrual cycle

Albrizio,

Desantis,

Lacitignola

et al. 2023

Vet Res Commun

View full text Add to dashboard Cite

The presence of HSPs in female reproductive and their relationship with the steroid hormone fluctuation have been reported in several mammals but not in non-human primates. The present research dealt with the oviductal expression and localization of the more studied HSPs (60, 70, and 90) as well as the morphological changes in the Hamadryas baboon (Papio hamadryas) during the follicular, preovulatory, and luteal phases of the menstrual cycle. Therefore, western blots, histomorphological, and immunohistochemical analyses were carried out. The results of western blot analysis displayed the lowest HSP expression in the luteal phase. The histomorphology showed that the mucosal epithelium consisted of undifferentiated cuboidal cells in follicular and luteal phases and well-distinguishable columnar ciliated and non-ciliated cells during the preovulatory phase. Immunohistochemistry evidenced that the mucosal epithelium contained cytoplasmic and nuclear HSP60, 70, and 90 immunostaining in the follicular and luteal phases. During the preovulatory phase, the non-ciliated cells showed: (i) cytoplasmic HSP60; (ii) nuclear and cytoplasmic HSP90. Ciliated cells showed cytoplasmic and ciliary HSP70 and ciliary HSP90. The stromal cells and myocytes of muscular layer displayed a decreased cytoplasmic HSP60 in the preovulatory phase and nuclear and low cytoplasmic HSP70 throughout the menstrual cycle. Nuclear HSP90 decreased in ampulla stromal cells and the follicular phase myocytes. These findings indicate that the expression pattern of HSP60,70, and 90 is related to the morphofunctional features of the baboon oviductal ampulla during the menstrual cycle and could represent a referent point for further studies in the oviduct of Primates.

show abstract

“…Hsp70 is present in all of the subcellular compartments of nucleated cells including cell membranes and, as an angiogenesis regulator, Hsp70 can activate ERK [ 59 ]. Hsp70 overexpression is associated with inhibition of apoptosis and tumor invasion, on the contrary, downregulation of Hsp70 leads to the demise of cancer cells [ 60 ]. With this in mind, it could be assumed that the modulation of the Hsp70 system found in DEX-treated MC3T3-E1 cells by returning to control levels upon colostrum exposure may constitute a mechanism for balancing proliferation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells

Martín‐Aragón

Bermejo-Bescós

Benedı́

et al. 2021

IJMS

View full text Add to dashboard Cite

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.

show abstract

Differential expression of angiogenesis markers HSP70, HSP90, VEGF and pERK1/2 in both components of dedifferentiated chondrosarcomas

Cited by 3 publications

References 38 publications

Distinct IDH1/2-associated Methylation Profile and Enrichment ofTP53andTERTMutations Distinguish Dedifferentiated Chondrosarcoma from Conventional Chondrosarcoma

Distinct IDH1/2-associated Methylation Profile and Enrichment ofTP53andTERTMutations Distinguish Dedifferentiated Chondrosarcoma from Conventional Chondrosarcoma

The abundance and localization of heat shock proteins (HSP)-60, -70, and -90 in the oviductal ampulla of hamadryas baboon (Papio hamadryas) during the menstrual cycle

A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells

Contact Info

Product

Resources

About