Calreticulin, an endoplasmic reticulum-resident protein, is highly expressed and essential for cell proliferation and migration in oral squamous cell carcinoma

Cellular immune responses play a critical role in the eradication of intracellular infections and malignant cells through the recognition and subsequent removal of the infection or malignant cells. Effective antigen presentation is crucial for stimulating the immune system against malignant cells. Calreticulin (CRT) has been used to improve antigen presentation. However, CRT overexpression has been previously associated with the development of pancreatic and breast cancer. The import and retention signals of CRT in the endoplasmic reticulum (ER) can be used to overcome CRT overexpression. The present study describes the potent antitumor effect of a DNA vaccine encoding human papillomavirus type 16 E6 and E7 antigens flanked by ER import and retention signals (SP-E6E7m-KDEL). The effect of this vaccine was compared with that of E6 and E7 antigens fused to human full-length CRT (hCRT-E6E7m). In the present study, the effectiveness of SP-E6E7m-KDEL for inducing an interferon-γ antigen-specific, response and its therapeutic effect against tumors was demonstrated, which was as effective as immunization against those antigens fused to CRT. This simplified strategy, using ER import and retention signal peptides to direct antigens to this organelle, provides an efficient alternative to traditional vaccines and, more importantly, a safe and potent system to induce a therapeutic antitumor response.

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“…Calcium mediates cell migration, and upregulation through transduction seriously affects cell invasiveness (31,32). …”

Section: Discussionmentioning

confidence: 99%

DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect

et al. 2017

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“…Elevated CALR expression promotes the migration and invasion of cancer cells (40). SENL treatment decreased CALR expression in LNCaP-luc2 and PC3 cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of the Supercritical Extract of Azadirachta Indica (Neem) Leaves In Vitro and In Vivo on Inhibition of Prostate Cancer Tumor Growth

Kohli

Bergen

et al. 2014

Molecular Cancer Therapeutics

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Azadirachta indica, commonly known as neem, has gained worldwide prominence because of its medical properties, namely antitumor, antiviral, anti-inflammatory, antihyperglycemic, antifungal, and antibacterial activities. Despite these promising results, gaps remain in our understanding of the molecular mechanism of action of neem compounds and their potential for use in clinical trials. We investigated supercritical extract of neem leaves (SENL) for the following: molecular targets in vitro, in vivo efficacy to inhibit tumor growth, and bioactive compounds that exert antitumor activity. Treatment of LNCaP-luc2 prostate cancer cells with SENL suppressed dihydrotestosterone-induced androgen receptor and prostate-specific antigen levels. SENL inhibited integrin β1, calreticulin, and focal adhesion kinase activation in LNCaP-luc2 and PC3 prostate cancer cells. Oral administration of SENL significantly reduced LNCaP-luc2 xenograft tumor growth in mice with the formation of hyalinized fibrous tumor tissue, reduction in the prostate-specific antigen, and increase in AKR1C2 levels. To identify the active anticancer compounds, we fractionated SENL by high-pressure liquid chromatography and evaluated 16 peaks for cytotoxic activity. Four of the 16 peaks exhibited significant cytotoxic activity against prostate cancer cells. Mass spectrometry of the isolated peaks suggested the compounds with cytotoxic activity were nimbandiol, nimbolide, 2′,3′-dihydronimbolide, and 28-deoxonim-bolide. Analysis of tumor tissue and plasma samples from mice treated with SENL indicated 28-deoxonim-bolide and nimbolide as the bioactive compounds. Overall, our data revealed the bioactive compounds in SENL and suggested that the anticancer activity could be mediated through alteration in androgen receptor and calreticulin levels in prostate cancer.

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“…Besides, calreticulin is also involved in the regulation of wound healing, tumorigenesis and immunity. Studies have also assessed the function of calreticulin in cell proliferation, revealing that it is highly expressed in several cancer types such as hepatoma, colon cancer and oral squamous cell carcinoma with increased cell proliferation (14,15). Furthermore, manipulation of calreticulin levels affected cancer cell proliferation, angiogenesis and differentiation (15).…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke extract promotes proliferation of airway smooth muscle cells through suppressing C/EBP-α expression

Guan

Cai²,

et al. 2017

Experimental and Therapeutic Medicine

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Cigarette smoke has been considered a major contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth muscle layer has been observed to be markedly thickened and the proliferation of airway smooth muscle cells (ASMCs) was therefore used by the present study as a model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed to various concentrations of CSE and the proliferation of the cells was analyzed by an MTT assay. Furthermore, the expression levels of calreticulin and CCAAT/enhancer-binding protein alpha (C/EBP-α) in CSE-stimulated ASMCs were determined by polymerase chain reaction and western blot analyses. In addition, the effects of RNA interference (RNAi) to knockdown calreticulin and/or C/EBP-α on ASMC proliferation were studied. CSE was found to promote the proliferation of ASMCs, which was associated with increased expression of calreticulin and decreased expression of C/EBP-α. Knockdown of calreticulin resulted in the upregulation of C/EBP-α and inhibition of cell proliferation, while simultaneous knockdown of C/EBP-α promoted cell proliferation. The present study revealed that CSE promoted the proliferation of ASMCs, which was mediated by inhibition of C/EBP-α. These findings shed new light on airway remodeling in COPD and may provide novel approaches for therapies.

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Calreticulin, an endoplasmic reticulum-resident protein, is highly expressed and essential for cell proliferation and migration in oral squamous cell carcinoma

Cited by 56 publications

References 45 publications

DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect

DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect

Preclinical Evaluation of the Supercritical Extract of Azadirachta Indica (Neem) Leaves In Vitro and In Vivo on Inhibition of Prostate Cancer Tumor Growth

Cigarette smoke extract promotes proliferation of airway smooth muscle cells through suppressing C/EBP-α expression

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