Altered Calreticulin expression in human colon cancer: Maintenance of Calreticulin expression is associated with mucinous differentiation

Abstract

Calreticulin is an endoplasmic reticulum luminal calcium-binding chaperone involved in various cellular functions and is a ligand for the scavenger receptor CD91. Recent studies, based on proteomic approaches on whole tissue samples containing both neoplastic and non-neoplastic cells, have shown alterations of Calreticulin expression in colon carcinomas, albeit with divergent results. The aims of this study were: 1) to assess the expression of Calreticulin and its receptor CD91 in 58 human colon adenocarcinomas, compared with paired normal mucosa, using a semi-quantitative immunohistochemical analysis, and 2) to examine associations between the tumour phenotypic features, and Calreticulin and/or CD91 expressions. Calreticulin expression was down-regulated in 51.7% human colon adenocarcinomas. Accordingly, quantitative immunoblot analysis showed that Calreticulin expression was significantly lower in human colonic cancer cell lines than in preparations of isolated human normal colonic epithelial cells. CD91 was co-expressed with Calreticulin in both normal colonic epithelial cells and pericryptic myofibroblasts. Calreticulin and CD91, that characterize the 'amateur phagocyte' function of epithelial cells, were both downregulated in 48% of adenocarcinomas. Finally, Calreticulin expression was significantly associated with the mucinous differentiation of the tumour. Collectively, these results show that Calreticulin is likely to play a pivotal role in the differentiation of human colonic adenocarcinomas.

Improved Clinical Outcome in Indolent B-Cell Lymphoma Patients Vaccinated with Autologous Tumor Cells Experiencing Immunogenic Death

“…Therefore, primary tumor cells may be less prone to undergo immunogenic cell death compared with in vitro established cell lines. Accordingly, the ability to downregulate CRT expression has been shown to be associated with a negative prognostic/predictive effect in colon cancer (28), neuroblastoma (29), and cervical carcinoma (30), as well as in follicular thyroid carcinoma (31). Nevertheless, our in vitro models consistently showed CRT and HSP90 cell surface translocation are the distinctive features induced by the combined exposure to HS, γ, and UVC.…”

Immunogenic death of colon cancer cells treated with oxaliplatin

“…First, the chemotherapeutic response will not only be dictated by the capacity of tumor cells to undergo apoptosis in response to OXP but will also be influenced by their intrinsic potential to emit immunogenic signals (such as CRT exposure and HMGB1 secretion). In this context, it seems intriguing that reduced calreticulin expression constitutes a negative prognostic/predictive feature of colon cancers (Toquet et al, 2007). Reduced calreticulin expression also has a negative impact on neuroblastoma (Hsu et al, 2005), cervical carcinoma (Mehta et al, 2008), as well as on follicular thyroid carcinoma (Netea-Maier et al, 2008).…”

CALR (calreticulin)

“…Similarly, Peng and colleagues (Peng, et al 2010) observed reduced expression of CALR in colon tumors in relation to adjacent normal epithelium; of note, CALR expression was associated with T-cell infiltration and better survival rates in colon cancer patients by univariate analysis. CALR downregulation was also observed in colonic cancer cell lines (SW1116, SW620, SW480, HT29, HT29-Cl.19A, HT29-Cl.16E and Colo320 cells) compared to primary normal colonic epithelial cells (Toquet, et al 2007). In contrast, Vougas and colleagues (Vougas, et al 2008) reported high CALR expression in colon cancer compared to the matched mirror biopsy tissues, especially in highly malignant and poorly differentiated tumors.…”

“…2017;21(3)nuclear matrix of colon cancer cells, though not of normal colon tissue (Brunagel, et al 2003). Low CALR expression was observed in colon cancer compared to normal colon tissue (Alfonso, et al 2005;Toquet, et al 2007). Similarly, Peng and colleagues (Peng, et al 2010) observed reduced expression of CALR in colon tumors in relation to adjacent normal epithelium; of note, CALR expression was associated with T-cell infiltration and better survival rates in colon cancer patients by univariate analysis.…”