Expression and significance of calreticulin in human osteosarcoma

Zhang, Xuhua; Zhang, Yue; Xie, Wen‐Peng; Sun, Desheng; Zhang, Yongkui; Hao, Yanke; Tan, Guoqing

doi:10.3233/cbm-160266

Cited by 11 publications

(11 citation statements)

References 22 publications

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“…Previous studies have demonstrated that CRT is upregulated in oral squamous cell carcinoma ( 11 ), pancreatic cancer ( 14 ), breast cancer ( 15 ), hepatocellular carcinoma ( 17 ), adrenocortical carcinomas ( 18 ) and gastric cancer ( 19 ). However, the results of a previous study by the present authors indicated that CRT was downregulated in osteosarcoma cells ( 20 ). In the present study, immunofluorescent staining, RT-qPCR and western blotting were conducted to detect the expression of CRT in Saos-2 osteosarcoma cells following culture with DATS at different concentrations and exposure times.…”

Section: Discussioncontrasting

confidence: 77%

“…A previous study conducted by the present research team demonstrated that DATS inhibited the proliferation of osteosarcoma cells and promoted their apoptosis in a dose- and time-dependent manner in vitro ( 25 ). Another study by the present research team ( 20 ) observed that the expression of CRT in patients with osteosarcoma was higher in the normal tissues surrounding the tumors than in the tumor tissues. In addition, CRT expression was greater in patients without metastasis than in those with metastasis, and in patients following chemotherapy than in those prior to chemotherapy.…”

Section: Discussionmentioning

confidence: 57%

“…Previous studies have demonstrated that CRT expression is closely associated with the occurrence, development, diagnosis, prognosis and response to therapy of various tumors ( 11 – 19 ); CRT has been shown to promote the growth of certain tumors, but to inhibit the growth of others. A previous study conducted by the present research team ( 20 ) identified that there was a strong association between low expression levels of CRT and osteosarcoma growth and metastasis, which suggests that CRT may serve as a potential drug target for osteosarcoma.…”

Section: Introductionmentioning

confidence: 59%

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Treatment of Saos‑2 osteosarcoma cells with diallyl trisulfide is associated with an increase in calreticulin expression

Xie

Zhang

et al. 2018

Exp Ther Med

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Diallyl trisulfide (DATS) is a natural organic sulfur compound that may be isolated from garlic and has strong anticancer activity. DATS has been demonstrated to upregulate the expression of calreticulin (CRT) in various types of human cancers, which is associated with the prognosis of cancer and its response to therapy. However, whether DATS has the same effect on human osteosarcoma cells is not known. Therefore, in the present study, Saos-2 human osteosarcoma cells were cultured with different concentrations of DATS (0, 25, 50 and 100 µmol/l) for 24 h, or with 50 µmol/l DATS for different time periods (0, 12, 24 and 36 h). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescent staining were used to detect CRT mRNA and protein in the Saos-2 cells. Exposure to DATS changed the morphology and inhibited the growth of the Saos-2 cells, and its effects appeared to be concentration- and exposure time-dependent. The optimum concentration and exposure time of DATS were 50 µmol/l and 24 h, respectively. The levels of CRT mRNA and protein in the Saos-2 cells were significantly upregulated following exposure to DATS. The upregulation of CRT expression by DATS may be a mechanism underlying the ability of DATS to inhibit the growth of human osteosarcoma Saos-2 cells.

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Section: Discussioncontrasting

confidence: 77%

Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 59%

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Treatment of Saos‑2 osteosarcoma cells with diallyl trisulfide is associated with an increase in calreticulin expression

Xie

Zhang

et al. 2018

Exp Ther Med

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“…In line with the extent of ER stress induced, we found that dox elicited ICD in sensitive osteosarcoma cells only, Ndox and Sdox in both sensitive and resistant cells. It has been reported that a high intratumor CRT is good prognostic factor in osteosarcoma patients [34] and that HMGB1 release is a marker of dox-induced necrosis [35]. Our work explains these findings, since we shows that CRT and HMGB1 increase are premises to trigger ICD in osteosarcoma and are proofs of dox's efficacy.…”

Section: Discussionsupporting

confidence: 73%

Novel anthracyclines with enhanced immunogenic effects against drug resistant osteosarcoma cells

2018

J. Mol. Clin. Med.

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Doxorubicin (dox) is one of the first-line drug treatment in osteosarcoma. P-glycoprotein (Pgp) limits dox's intracellular accumulation and efficacy in osteosarcoma. Part of the cytotoxic effects of dox are mediated by the induction of immunogenic cell death (ICD) that allows a durable eradication of the tumor by the host immune system. Pgp-overexpressing tumors, however, are also ICD-resistant. We recently synthesized two classes of synthetic doxs -nitric oxide (NO)-releasing dox and H 2 S-releasing doxthat were cytotoxic against different Pgp-expressing tumors. The aim of this work is to investigate if the lead compounds (termed Ndox and Sdox) were able to elicit ICD in Pgp-positive/dox-resistant osteosarcoma cells. Ndox and Sdox induced apoptosis in both sensitive and resistant cells, were localized within the endolasmic reticulum (ER), up-regulated ER stress-dependent cell death genes, promoted the translocation of calreticulin form ER to cell surface, induced the extracellular release of ATP and HMGB1, increased the phagocytosis of tumor cells by dendritic cells and the expansion of anti-tumor CD8 + T-lymphocytes, in a NO-and H 2 S-dependent manner, respectively. Expanded CD8 + clones up-regulated immune-activating cytokines and down-regulated immune-suppressive cytokines. Dox induced the same events in sensitive cells, but not in Pgp-expressing/doxresistant cells. We suggest Ndox and Sdox as new multifunctional anthracyclines able to induce apoptosis of resistant osteosarcoma cells and contemporarily activate an anti-tumor immune response. These pro-drugs may have a future use in osteosarcoma patients with high Pgp expression, characterized by a poor outcome because of the lack of durable tumor eradication and the high frequency of relapse.

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“…Several chaperone proteins are known to activate integrins, including talin [ 2 ], kindlin-1 and kindlin-2 [ 3 ], and calreticulin (CALR) [ 4 , 5 ]. In this study, we focus on CALR, since several studies have revealed a connection between disruption of CALR function and various malignancies including myeloproliferative disorders [ 6 ], osteocarcoma [ 7 ], ovarian and non-small cell lung cancer [ 8 ], breast cancer [ 9 ], and Glioblastoma (GBM) [ 10 ]. CALR was first identified in 1974 by Ostwald and MacLennan [ 11 ] and has been extensively studied for over 40 years.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone-Mediated Upregulation of Calreticulin Inhibits Primary Human Glioblastoma Dispersal Ex Vivo

Nair

Romero

Mahtabfar

et al. 2018

IJMS

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Dispersal of Glioblastoma (GBM) renders localized therapy ineffective and is a major cause of recurrence. Previous studies have demonstrated that Dexamethasone (Dex), a drug currently used to treat brain tumor–related edema, can also significantly reduce dispersal of human primary GBM cells from neurospheres. It does so by triggering α5 integrin activity, leading to restoration of fibronectin matrix assembly (FNMA), increased neurosphere cohesion, and reduction of neurosphere dispersal velocity (DV). How Dex specifically activates α5 integrin in these GBM lines is unknown. Several chaperone proteins are known to activate integrins, including calreticulin (CALR). We explore the role of CALR as a potential mediator of Dex-dependent induction of α5 integrin activity in primary human GBM cells. We use CALR knock-down and knock-in strategies to explore the effects on FNMA, aggregate compaction, and dispersal velocity in vitro, as well as dispersal ex vivo on extirpated mouse retina and brain slices. We show that Dex increases CALR expression and that siRNA knockdown suppresses Dex-mediated FNMA. Overexpression of CALR in GBM cells activates FNMA, increases compaction, and decreases DV in vitro and on explants of mouse retina and brain slices. Our results define a novel interaction between Dex, CALR, and FNMA as inhibitors of GBM dispersal.

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Expression and significance of calreticulin in human osteosarcoma

Abstract: These results could indicate a brand-new biological marker which may be applied to estimate the features and prognosis of osteosarcoma.

Cited by 11 publications

References 22 publications

Treatment of Saos‑2 osteosarcoma cells with diallyl trisulfide is associated with an increase in calreticulin expression

Treatment of Saos‑2 osteosarcoma cells with diallyl trisulfide is associated with an increase in calreticulin expression

Novel anthracyclines with enhanced immunogenic effects against drug resistant osteosarcoma cells

Dexamethasone-Mediated Upregulation of Calreticulin Inhibits Primary Human Glioblastoma Dispersal Ex Vivo

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