Zhongli Wang1, Chao Liu. 1. Department of General Surgery, the First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, People's Republic of China.
Abstract
BACKGROUND/AIMS: Effective treatment of gastric cancer (GC) requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs) in GC appears to be a critical question. METHODS: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA) to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. RESULTS: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. CONCLUSION: Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome.
BACKGROUND/AIMS: Effective treatment of gastric cancer (GC) requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs) in GC appears to be a critical question. METHODS: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA) to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. RESULTS: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. CONCLUSION:Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome.
Authors: Maria Laura Martin; Zhaoshi Zeng; Mohammad Adileh; Adrian Jacobo; Christy Li; Efsevia Vakiani; Guoqiang Hua; Lixing Zhang; Adriana Haimovitz-Friedman; Zvi Fuks; Richard Kolesnick; Philip B Paty Journal: Cell Signal Date: 2017-09-25 Impact factor: 4.315
Authors: A Fatehullah; Y Terakado; S Sagiraju; T L Tan; T Sheng; S H Tan; K Murakami; Y Swathi; N Ang; R Rajarethinam; T Ming; P Tan; B Lee; N Barker Journal: Nat Cell Biol Date: 2021-12-02 Impact factor: 28.824