Calreticulin exposure increases cancer immunogenicity

Clarke, Chris J P; Smyth, Mark J.

doi:10.1038/nbt0207-192

Cited by 75 publications

(58 citation statements)

References 7 publications

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“…It is not consistent with other studies that showed SMMC-7721 treated with Tan-IIA was arrested at the G0/G1 phase (15). ER stress-associated apoptotic molecules such as Calreticulin, caspase 12 and GADD153 are important key factors (23)(24)(25). Our results show that Hep-J5 cells treated with Tan-IIA increased the protein expression of calreticulin, caspase 12 and GADD153.…”

Section: Discussioncontrasting

confidence: 41%

Tanshinone IIA inhibits Hep-J5 cells by increasing calreticulin, caspase 12 and GADD153 protein expression

Cheng

Su²

2010

Int J Mol Med

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Abstract. Tanshinone IIA (Tan-IIA) is extracted from Danshen, Salviae miltiorrhizae Radix, which has been widely adopted in traditional herbal medicine to treat cardiovascular and hepatic diseases. Tan-IIA induces apoptosis and inhibits proliferation in human hepatocellular carcinoma (HCC) cells. However, the molecular mechanisms of Tan-IIA on human HCC cells are not understood clearly. In the present study, the cytotoxicity of Tan-IIA as well as its molecular mechanisms in human HCC J5 cells was investigated. The cytotoxicity was assayed by MTT. The protein expression of p53, p21, Bax, Bcl-2, Cdc25c, Cdc2, calreticulin, caspase 12, GADD153, caspase 3 and ß-actin in J5 cells were determined by Western blotting. The cell cycles were analyzed by FACS. The protein expression of caspase 12, GADD1533 and caspase 3 were detected by immunocytochemical staining. The results showed that Tan-IIA inhibited J5 cells in a dose-and timedependent manner. The protein expression of p53, p21, Bax, calreticulin, caspase 12, caspase 3 and GADD153 were increased, but Bcl-2, Cdc25c and Cdc2 were decreased in J5 cells. In addition, the results also showed that Tan-IIA arrested J5 cells in the G2/M phase. Immunocytochemistry staining showed that J5 cells treated with Tan-IIA up-regulated the protein expression of caspase 12, 3 and GADD153. Taken together, the findings suggest that Tan-IIA inhibits and induces apoptosis in J5 cells through novel molecular targets, calreticulin, caspase 12 and GADD153.

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Section: Discussioncontrasting

confidence: 41%

Tanshinone IIA inhibits Hep-J5 cells by increasing calreticulin, caspase 12 and GADD153 protein expression

Cheng

Su²

2010

Int J Mol Med

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“…S3H). Previous studies have shown that macrophages engulf dead cells to trigger adaptive immune responses through antigen presentation to T cells, and regulate the tumor microenvironment by producing immune mediators in response to cancer (33). It was recently suggested that macrophages phagocytose living cancer cells and suppress tumor development (26,34), although the molecular mechanism for this remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis

Kimura

Inoue

Hangai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Tumor metastasis is the cause of most cancer deaths. Although metastases can form in multiple end organs, the liver is recognized as a highly permissive organ. Nevertheless, there is evidence for immune cell-mediated mechanisms that function to suppress liver metastasis by certain tumors, although the underlying mechanisms for the suppression of metastasis remain elusive. Here, we show that Dectin-2, a C-type lectin receptor (CLR) family of innate receptors, is critical for the suppression of liver metastasis of cancer cells. We provide evidence that Dectin-2 functions in resident macrophages in the liver, known as Kupffer cells, to mediate the uptake and clearance of cancer cells. Interestingly, Kupffer cells are selectively endowed with Dectin-2-dependent phagocytotic activity, with neither bone marrow-derived macrophages nor alveolar macrophages showing this potential. Concordantly, subcutaneous primary tumor growth and lung metastasis are not affected by the absence of Dectin-2. In addition, macrophage C-type lectin, a CLR known to be complex with Dectin-2, also contributes to the suppression of liver metastasis. Collectively, these results highlight the hitherto poorly understood mechanism of Kupffer cell-mediated control of metastasis that is mediated by the CLR innate receptor family, with implications for the development of anticancer therapy targeting CLRs.liver metastasis | C-type lectin receptor | Dectin-2 | Kupffer cell | phagocytosis

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“…The mechanistic pathways involving calreticulin and its role in cancer remains largely unknown, although there have been extensive reports about the role of calreticulin in immunogenic cell death of cancerous cells as translocation of calreticulin together with ERp57 to the cell surface was found to be essential for death of cancer cells [33][34][35] in response to treatment with anthracycline [36][37][38] or exposure to UV light or g irradiation. 39 Calreticulin has also been implicated in another pathway of cell death known as anoikis, which is a necessary cell death program for anchorage-dependent cells.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of calreticulin in breast invasive ductal carcinoma

et al. 2010

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Calreticulin is a chaperone protein located in the lumen of the endoplasmic reticulum. The association of calreticulin with pathological conditions such as autoimmune disorders and certain types of cancer have been reported. However, little is known about its role in the pathogenesis of breast cancer. The aim of this study was to determine the expression of calreticulin in vitro and correlate its expression levels in breast cancer tissue samples with clinicopathological parameters. Calreticulin expression was evaluated in MCF-7 and MDA-MB-231 breast cancer cells by real-time RT-PCR, Western blot, immunohistochemistry, and immunofluorescence staining. Patient tissue microarrays were constructed from 228 breast cancer specimens for immunohistochemical analysis. The in vitro study showed a higher calreticulin expression in more aggressive MDA-MB-231 cells as compared with MCF-7 cells at both mRNA and protein levels. In all, 227 out of 228 breast cancer samples exhibited calreticulin staining in at least 5% of the cancer cells. Calreticulin immunostaining was observed to be localized to the cytoplasm of the cancer cells. Regression analysis of calreticulin immunostaining in the tissue microarrays revealed that its expression was positively correlated to logarithm of (log) tumor size (P ¼ 0.046) and development of distant metastasis (P ¼ 0.017). Multivariate analysis confirmed calreticulin expression as an independent predictor of log tumor size and occurrence of distant metastasis. The data suggest that calreticulin expression is associated with more advanced tumors and is a potential prognostic biomarker.

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Calreticulin exposure increases cancer immunogenicity

Cited by 75 publications

References 7 publications

Tanshinone IIA inhibits Hep-J5 cells by increasing calreticulin, caspase 12 and GADD153 protein expression

Tanshinone IIA inhibits Hep-J5 cells by increasing calreticulin, caspase 12 and GADD153 protein expression

The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis

Clinicopathological significance of calreticulin in breast invasive ductal carcinoma

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