Photodynamic Therapy-mediated Cancer Vaccination Enhances Stem-like Phenotype and Immune Escape, Which Can Be Blocked by Thrombospondin-1 Signaling through CD47 Receptor Protein

Zheng, Yang; Zou, Fangyuan; Wang, Jingjing; Yin, Guifang; Le, Vanminh; Fei, Zhewei; Liu, Jianwen

doi:10.1074/jbc.m114.624965

Cited by 18 publications

(11 citation statements)

References 51 publications

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“…PTB-targeting pSilencer plasmid was constructed as described in the previous report (Zheng et al , 2015). Briefly, p Silencer 2.1-U6 Neo vector and the non-targeting control plasmid were purchased from Invitrogen.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

et al. 2017

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Background:Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of PTBP3 suppressed the proliferation and differentiation of gastric cancer cells in vivo.Methods:PTBP3 mRNA levels in human gastric cancer and adjuvant non-tumour tissues were detected. Apoptosis and 5-FU effect were determined in PTBP3-silenced gastric cancer cells. Underlying molecular mechanisms were investigated.Results:MRNA expression of PTBP3 was upregulated in gastric cancer tissues, especially in those at an advanced stage. PTBP3 silencing led to apoptosis, under which modulation of PTB and thereby switch of Bcl-x pre-mRNA splicing pattern might be an important mechanism. Further research found that inhibition of PTBP3 expression enhanced the chemosensitivity of gastric cancer cells towards 5-FU treatment. This was mediated by reduced expression of histone deacetylase 6 (HDAC6), which further inhibited the phosphorylation of Akt and the expression of thymidylate synthase (TYMS), the critical determinant of 5-FU cytotoxicity.Conclusions:PTBP3 might serve as a biomarker of gastric cancer or potential target for anti-cancer therapy.

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Section: Methodsmentioning

confidence: 99%

Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

et al. 2017

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“…As one of several functions, CD47 serves as the ligand for TSP 294 that expressed on the surface of phagocytic cells, including 295 macrophages and dendritic cells [19,20]. The interaction of 296 CD47 and TSP initiates a signal transduction cascade, resulting 297…”

Section: Tsp Promotes Its Interaction With Crt and Cd47mentioning

confidence: 99%

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

Chen

Xiao-ming

Jiang

et al. 2015

Biomedicine & Pharmacotherapy

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“…Repeated passage in immune-competent mice to select resistant cells from Lewis lung carcinoma resulted in the isolation of cells with increased CSC characteristics as well as increased CD47 expression (Zheng et al, 2015). Notably, the selected cells also had very low TSP1 expression.…”

Section: Cd47 In Cancer Stem Cellsmentioning

confidence: 99%

“…Notably, knockdown of CD47 using a shRNA vector blocked these responses to TSP1. TSP1 treatment also inhibited proliferation and suppressed sphere formation in human colon cancer (HCT116), non-small cell lung cancer (A549), and cervical cancer (HeLa) cell lines (Zheng, 2015). These data further support a cell-autonomous function of CD47 signaling in CSCs and implicate TSP1 signaling through CD47 in regulating CSC fate.…”

Section: Cd47 In Cancer Stem Cellsmentioning

confidence: 99%

“…We have shown that Burkitt’s lymphoma cells, where the 5’ promoter region of cMyc is replaced with Ig heavy chain promoter sequence, are resistant to growth inhibition by CD47 over-expression, and cMyc expression is unperturbed by CD47 in these cells (Kaur, 2013). Others have identified NFκB dependent regulation of cystatin-S/protease activated receptor-2, p21, Gβγ-dependent activation of the PI3-kinase/Akt pathway, and ubiquitin-like with PHD and ring finger domains 1 (UHRF1)-dependent down-regulation of p16 INK4A as targets of CD47 signaling in specific cancer cell lines (Boukhari et al, 2015; Lee, 2014b; Sick et al, 2011; Zheng, 2015). Further study is needed to determine which of these CD47 target pathways generalize to other cancer types, and which may differ in neoplastic versus nontransformed stem cells.…”

Section: Future Prospectsmentioning

confidence: 99%

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Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling

Kaur

Roberts

2016

The International Journal of Biochemistry & Cell Biology

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Thrombospondin-1 is a secreted matricellular protein that regulates the differentiation and function of many cell types. Thrombospondin-1 is not required for embryonic development, but studies using lineage-committed adult stem cells have identified positive and negative effects of thrombospondin-1 on stem cell differentiation and self-renewal and identified several thrombospondin-1 receptors that mediate these responses. Genetic studies in mice reveal a broad inhibitory role of thrombospondin-1 mediated by its receptor CD47. Cells and tissues lacking thrombospondin-1 or CD47 exhibit an increased capacity for self-renewal associated with increased expression of the stem cell transcription factors c-Myc, Sox2, Klf4, and Oct4. Thrombospondin-1 inhibits expression of these transcription factors in a CD47-dependent manner. However, this regulation differs in some neoplastic cells. Tumor initiating/cancer stem cells express high levels of CD47, but in contrast to nontransformed stem cells CD47 signaling supports cancer stem cells. Suppression of CD47 expression in cancer stem cells or ligation of CD47 by function blocking antibodies or thrombospondin-1 results in loss of self-renewal. Therefore, the therapeutic CD47 antagonists that are in clinical development for stimulating innate anti-tumor immunity may also inhibit tumor growth by suppressing cancer stem cells. These and other therapeutic modulators of thrombospondin-1 and CD47 signaling may also have applications in regenerative medicine to enhance the function of normal stem cells.

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Photodynamic Therapy-mediated Cancer Vaccination Enhances Stem-like Phenotype and Immune Escape, Which Can Be Blocked by Thrombospondin-1 Signaling through CD47 Receptor Protein

Cited by 18 publications

References 51 publications

Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

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

Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling

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