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Regulation of CD47 expression in cancer cells.

ABSTRACT: CD47 is overexpressed in various types of cancers and it can directly bind with SIRP?, which is mainly located on macrophages. The binding of CD47-SIRP? transmits a "don't eat me" signal, which can prevent cancer cells from immune clearance. Targeting the phagocytosis checkpoint of CD47-SIRP? axis has shown remarkable anticancer effect in preclinical and clinical research, which indicates the potential application of CD47-SIRP? blockade for cancer treatment. In this case, the comprehensive description of the regulation of CD47 in different types of cancer cells has significant implications for furthering our understanding of the role of CD47 in cancer. Based on the current reports, we summarized the regulatory factors, i.e., cytokines, oncogenes, microRNAs as well as enzymes, of CD47 expression in cancer cells. Accordingly, we also proposed several points needing further research, hoping to provide useful insights for the future investigation on the regulation of CD47 in cancers.

SUBMITTER: Huang CY

PROVIDER: S-EPMC7494507 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Regulation of CD47 expression in cancer cells.

Huang Can-Yu CY Ye Zi-Han ZH Huang Mu-Yang MY Lu Jin-Jian JJ

Translational oncology 20200910 12

CD47 is overexpressed in various types of cancers and it can directly bind with SIRPα, which is mainly located on macrophages. The binding of CD47-SIRPα transmits a "don't eat me" signal, which can prevent cancer cells from immune clearance. Targeting the phagocytosis checkpoint of CD47-SIRPα axis has shown remarkable anticancer effect in preclinical and clinical research, which indicates the potential application of CD47-SIRPα blockade for cancer treatment. In this case, the comprehensive descr ...[more]

PMID: 32920329

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Project description:Integrin-associated protein (CD47) is ubiquitously expressed on the surface of cells and functions as an identifier of self. In blood cancer, tumor cells expressing CD47 evade phagocytosis by macrophages, leading to a poor patient prognosis. However, the status of CD47 expression in solid tumors, particularly in gastric cancer, is not well understood. The purpose of the present study was to examine the level of CD47 in the primary tumor, peripheral blood (PB) and bone marrow (BM) of patients with gastric cancer, and to determine its effect. Reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the level of CD47 mRNA expression in primary tumor, PB and BM samples collected from 168 patients with gastric cancer. Cell sorting was performed to investigate CD47 protein expression in PB and BM fractions, and to identify the source of CD47 expression. In primary tumors, the expression of CD47 was not associated with any clinicopathological factors or prognosis. By contrast, in PB, the low CD47 expression group demonstrated a significantly increased tumor size, and frequency of lymphatic invasion and lymph node metastasis, compared with the high CD47 expression group. In addition, the clinical tumor stage of the low CD47 expression group was significantly increased compared with that of the high CD47 expression group. Conversely, in PB, the high CD47 expression group had a significantly higher frequency of lymphatic invasion and lymph node metastasis compared with the low CD47 expression group. The lymphocyte fraction exhibited the highest CD47 expression compared with the other fractions in PB and BM samples. Low expression of CD47 was associated with the advancement of gastric cancer, in contrast to other cancers, and it may be associated with a decrease in lymphocytes during later stages. These results indicate that CD47 expression in the PB and BM may serve as a marker to analyze the immunological function of patients with gastric cancer; however, the significance of CD47 in gastric cancer requires further study.

Project description:Under healthy conditions, pro- and anti-phagocytic signals are balanced. Cluster of Differentiation 47 (CD47) is believed to act as an anti-phagocytic marker that is highly expressed on multiple types of human cancer cells including acute myeloid leukemia (AML) and lung and liver carcinomas, allowing them to escape phagocytosis by macrophages. Downregulating CD47 on cancer cells discloses calreticulin (CRT) to macrophages and recovers their phagocytic activity. Herein, we postulate that using a modified graphene oxide (GO) carrier to deliver small interfering RNA (siRNA) CD47 (CD47_siRNA) in AML, A549 lung, and HepG2 liver cancer cells in co-culture in vitro will silence CD47 and flag cancer cells for CRT-mediated phagocytosis. Results showed a high knockdown efficiency of CD47 and a significant increase in CRT levels simultaneously by using GO formulation as carriers in all used cancer cell lines. The presence of CRT on cancer cells was significantly higher than levels before knockdown of CD47 and was required to achieve phagocytosis in co-culture with human macrophages. Lipid nanoparticles (LNPs) and modified boron nitride nanotubes (BNPs) were used to carry CD47_siRNA, and the knockdown efficiency values of CD47 were compared in three cancer cells in co-culture, with an achieved knockdown efficiency of >95% using LNPs as carriers. Interestingly, the high efficiency of CD47 knockdown was obtained by using the LNPs and BNP carriers; however, an increase in CRT levels on cancer cells was not required for phagocytosis to happen in co-culture with human macrophages, indicating other pathways' involvement in the phagocytosis process. These findings highlight the roles of 2D (graphene oxide), 1D (boron nitride nanotube), and "0D" (lipid nanoparticle) carriers for the delivery of siRNA to eliminate cancer cells in co-culture, likely through different phagocytosis pathways in multiple types of human cancer cells. Moreover, these results provide an explanation of immune therapies that target CD47 and the potential use of these carriers in screening drugs for such therapies in vitro.

Dataset Information

Regulation of CD47 expression in cancer cells.

Publications

Regulation of CD47 expression in cancer cells.

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