Thrombospondin promoted anti-tumor of adenovirus-mediated calreticulin in breast cancer: Relationship with anti-CD47

Chen, Qifeng; Xiao-ming, Fang; Jiang, Chaohui; Yao, Ning; Fang, Xudong

doi:10.1016/j.biopha.2015.05.017

Cited by 18 publications

(13 citation statements)

References 21 publications

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“…51 Indeed, recently, it was determined that treatment of breast cancer cell lines with thrombospondin-1 (TSP-1) promoted interaction of TSP-1 with CRT and CD47 and induced cell autophagy and tumor growth inhibition in xenografted mice. 52 These results support the idea that TSP-1 or peptides derived from TSP-1 can induce cell death through CD47 activation and its correlation with CRT exposure. Also, HSP70 and HSP90, HMGB1 and ATP were released by PKHB1 treatment on CEM, MOLT-4 and L5178Y-R cell lines (Figures 6,7).…”

Section: Discussionsupporting

confidence: 80%

“…There is a tight correlation between CRT and CD47 expression in cancer cells . Indeed, recently, it was determined that treatment of breast cancer cell lines with thrombospondin‐1 (TSP‐1) promoted interaction of TSP‐1 with CRT and CD47 and induced cell autophagy and tumor growth inhibition in xenografted mice . These results support the idea that TSP‐1 or peptides derived from TSP‐1 can induce cell death through CD47 activation and its correlation with CRT exposure.…”

Section: Discussionmentioning

confidence: 71%

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CD47 agonist peptide PKHB1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

et al. 2018

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T‐cell acute lymphoblastic leukemia (T‐ALL) has a poor prognosis derived from its genetic heterogeneity, which translates to a high chemoresistance. Recently, our workgroup designed thrombospondin‐1‐derived CD47 agonist peptides and demonstrated their ability to induce cell death in chronic lymphocytic leukemia. Encouraged by these promising results, we evaluated cell death induced by PKHB1 (the first‐described serum‐stable CD47‐agonist peptide) on CEM and MOLT‐4 human cell lines (T‐ALL) and on one T‐murine tumor lymphoblast cell‐line (L5178Y‐R), also assessing caspase and calcium dependency and mitochondrial membrane potential. Additionally, we evaluated selectivity for cancer cell lines by analyzing cell death and viability of human and murine non‐tumor cells after CD47 activation. In vivo, we determined that PKHB1‐treatment in mice bearing the L5178Y‐R cell line increased leukocyte cell count in peripheral blood and lymphoid organs while recruiting leukocytes to the tumor site. To analyze whether CD47 activation induced immunogenic cell death (ICD), we evaluated damage‐associated molecular patterns (DAMP) exposure (calreticulin, CRT) and release (ATP, heat shock proteins 70 and 90, high‐mobility group box 1, CRT). Furthermore, we gave prophylactic antitumor vaccination, determining immunological memory. Our data indicate that PKHB1 induces caspase‐independent and calcium‐dependent cell death in leukemic cells while sparing non‐tumor murine and human cells. Moreover, our results show that PKHB1 can induce ICD in leukemic cells as it induces CRT exposure and DAMP release in vitro, and prophylactic vaccinations inhibit tumor establishment in vivo. Together, our results improve the knowledge of CD47 agonist peptides potential as therapeutic tools to treat leukemia.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 71%

CD47 agonist peptide PKHB1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

et al. 2018

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“…In this sense, blocking CD47-SIRPa signal transduction by monoclonal antibodies or fusion proteins could increase macrophage phagocytosis of cancer cells. Blockade of the CD47/SIRPa axis by monoclonal antibody is a potential immunotherapeutic strategy for acute myeloid leukemia (13), breast cancer (14), and small cell lung cancer (15). CD47 is also highly expressed on NSCLC cells (16,17).…”

Section: Introductionmentioning

confidence: 99%

Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non–Small Cell Lung Cancer

Zhang

Fan

Wang

et al. 2017

Cancer Immunology Research

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CD47-specific antibodies and fusion proteins that block CD47-SIRPa signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in nonsmall cell lung cancer (NSCLC). SIRPaD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux, including formation and accumulation of autophagosomes, fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes. Meanwhile, reactive oxygen species and inactivation of mTOR were shown to be involved in autophagy initiation in SIRPaD1-Fc-treated cells, indicating a probable mechanism for autophagy activation after targeting CD47 by SIRPaD1-Fc. Inhibition of autophagy enhanced macrophage-mediated phagocytosis and cytotoxicity against SIRPaD1-Fc-treated NSCLC cells. In addition, simultaneously targeting both CD47 and autophagy in NSCLC xenograft models elicited enhanced antitumor effects, with recruitment of macrophages, activated caspase-3, and overproduction of ROS at the tumor site. Our data elucidated the cytoprotective role of autophagy in CD47-targeted therapy and highlighted the potential approach for NSCLC treatment by simultaneously targeting CD47 and autophagy.

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“…CRT was also highly expressed in oral squamous cell carcinoma tumor tissues and oral squamous cell carcinoma (OSCC) cell lines [ 32 ]. CRT expression was enhanced in the breast cancer cell lines MCF-7 and MDA-MB-231 compared with the normal breast epithelial cell line MCF-10A [ 33 ]. Diallyl disulfide treatment tremendously transformed the morphology of human promyelocytic leukemia HL-60 cells and created a vastly time-dependent downregulation of CRT [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays

Liang

Yin

et al. 2017

PLoS ONE

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The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received <50, 50–500, and 500–1000 μGy/h of 137Cs radiation for 180 d. We found that the pathological changes in liver tissues were more obvious as the irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.

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Thrombospondin promoted anti-tumor of adenovirus-mediated calreticulin in breast cancer: Relationship with anti-CD47

Cited by 18 publications

References 21 publications

CD47 agonist peptide PKHB1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

CD47 agonist peptide PKHB1 induces immunogenic cell death in T‐cell acute lymphoblastic leukemia cells

Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non–Small Cell Lung Cancer

Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays

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