scholarly journals Inflammation-Related DNA Damage and Cancer Stem Cell Markers in Nasopharyngeal Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Shumin Wang ◽  
Ning Ma ◽  
Weilin Zhao ◽  
Kaoru Midorikawa ◽  
Shosuke Kawanishi ◽  
...  

Nitrative and oxidative DNA damage plays an important role in inflammation-related carcinogenesis. To investigate the involvement of stem cells in Epstein-Barr virus infection-related nasopharyngeal carcinoma (NPC), we used double immunofluorescence staining to examine several cancer stem/progenitor cell markers (CD44v6, CD24, and ALDH1A1) in NPC tissues and NPC cell lines. We also measured 8-nitroguanine formation as an indicator of inflammation-related DNA lesions. The staining intensity of 8-nitroguanine was significantly higher in cancer cells and inflammatory cells in the stroma of NPC tissues than in chronic nasopharyngitis tissues. Expression levels of CD44v6 and ALDH1A1 were significantly increased in cancer cells of primary NPC specimens in comparison to chronic nasopharyngitis tissues. Similarly, more intense staining of CD44v6 and ALDH1A1 was detected in an NPC cell line than in an immortalized nasopharyngeal epithelial cell line. In the case of CD24 staining, there was no significant difference between NPC and chronic nasopharyngitis tissues. 8-Nitroguanine was detected in both CD44v6- and ALDH1A1-positive stem cells in NPC tissues. In conclusion, CD44v6 and ALDH1A1 are candidate stem cell markers for NPC, and the increased formation of DNA lesions by inflammation may result in the mutation of stem cells, leading to tumor development in NPC.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Min Thura ◽  
Zu Ye ◽  
Abdul Qader Al-Aidaroos ◽  
Qiancheng Xiong ◽  
Jun Yi Ong ◽  
...  

AbstractPRL3, a unique oncotarget, is specifically overexpressed in 80.6% of cancers. In 2003, we reported that PRL3 promotes cell migration, invasion, and metastasis. Herein, firstly, we show that PRL3 induces Polyploid Giant Cancer Cells (PGCCs) formation. PGCCs constitute stem cell-like pools to facilitate cell survival, chemo-resistance, and tumor relapse. The correlations between PRL3 overexpression and PGCCs attributes raised possibilities that PRL3 could be involved in PGCCs formation. Secondly, we show that PRL3+ PGCCs co-express the embryonic stem cell markers SOX2 and OCT4 and arise mainly due to incomplete cytokinesis despite extensive DNA damage. Thirdly, we reveal that PRL3+ PGCCs tolerate prolonged chemotherapy-induced genotoxic stress via suppression of the pro-apoptotic ATM DNA damage-signaling pathway. Fourthly, we demonstrated PRL3-zumab, a First-in-Class humanized antibody drug against PRL3 oncotarget, could reduce tumor relapse in ‘tumor removal’ animal model. Finally, we confirmed that PGCCs were enriched in relapse tumors versus primary tumors. PRL3-zumab has been approved for Phase 2 clinical trials in Singapore, US, and China to block all solid tumors. This study further showed PRL3-zumab could potentially serve an ‘Adjuvant Immunotherapy’ after tumor removal surgery to eliminate PRL3+ PGCC stem-like cells, preventing metastasis and relapse.


2010 ◽  
Vol 289 (2) ◽  
pp. 208-216 ◽  
Author(s):  
Shaker A. Mousa ◽  
Thangirala Sudha ◽  
Evgeny Dyskin ◽  
Usawadee Dier ◽  
Christine Gallati ◽  
...  

1998 ◽  
Vol 10 (8) ◽  
pp. 551 ◽  
Author(s):  
Martin F. Pera ◽  
Daniella Herszfeld

Pluripotent human teratocarcinoma stem cells cultured in vitro provide a resource for the study of early embryonic development in man, as well as a means for discovery of novel factors controlling cell differentiation and commitment. We previously reported that the human teratocarcinoma stem cell line GCT 27X-1 could be induced to differentiate into an endodermal progenitor cell by treatment with high doses of retinoic acid. A search for polypeptide inducers of differentiation in this system has identified bone morphogenetic protein-2 (BMP-2) as a potent inducer of differentiation. In cell line GCT 27X-1, treatment with BMP-2 reduces proliferation, induces morphological changes similar to obtained following treatment with retinoic acid, and causes a decrease in the expression of transcripts for the stem cell markers CD30 and Oct-4. Preliminary immunochemical studies indicate that the differentiated cells produced by BMP-2 are endodermal precursors with a pattern of marker expression similar to that found in retinoic acid treated cells. Models of endoderm differentiation in humans will be useful for identifying the molecules which mediate cell interactions in development, and in achieving directed differentiation of cells for use in transplantation.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S175-S175
Author(s):  
X R Wu ◽  
C Zhou ◽  
H S Liu ◽  
L Xuan-hui ◽  
T Hu ◽  
...  

Abstract Background The application of stem cell therapy in the treatment of inflammatory bowel diseases (IBD) is limited because of the invasive approaches of stem cells. Urine-derived stem cells (USCs) were recently shown to have regenerative properties, which can be harvested in a safe, low-cost and non-invasive way. Methods Human USC were isolated and expanded from the urine of healthy male adult volunteers (n = 3, age arrange 24–30 years old). USC were characterised by cell surface marker expression profile and multipotent differentiation. In vivo therapeutic value of USC was assessed using murine colitis chronic model induced by dextran sulphate sodium (DSS). Results USC were positive for mesenchymal stem cell markers but were negative for hematopoietic stem cell markers. These cells differentiated into osteo-, adipo- and chondro-genic cell lineages. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in chronic murine colitis model. Conclusion This study demonstrated that implantation of USC reduces inflammation in IBD rodent model, indicating that USC therapy serves as a potential cell-based therapeutic candidate for IBD.


Sign in / Sign up

Export Citation Format

Share Document