ABSTRACT
@#[Abstract] Objective: To investigate the effect of 18H12, a functional monoclonal antibody that can target gastric cancer stem cells, on the self-renewal and invasion ability of gastric cancer cells. Methods: The gastric cancer cell line PAMC-82 was used as cell model, the expression of ENO1 (enolase-1) on the membrane surface of its parental cells and enriched stem cells by sphere culture was detected by Flow cytometry. Flow cytometry was used to separate ENO1+ cells and ENO1- cells to detect their self-renewal ability and invasion ability. With the commercial ENO1 antigen and antibody as the samples, CoIP (co-immunoprecipitation) was used to verify whether 18H12 antibody targeting ENO1 could able to accurately recognize ENO1. After being treated with 18H12 for 12 h, 24 h and 48 h, the selfrenewal and invasion ability of PAMC-82 cells were detected by methylcellulose pelletization experiment and Transwell chamber assay, respectively. Results: Flow cytometry showed that the expression of ENO1 on the membrane surface of PAMC-82 sphere cells was significantly higher than that of its parental cells (P<0.01), so ENO1 could be a potential target for targeting gastric cancer stem cells. The self-renewal ability and invasion ability of the sorted ENO1+ cells were significantly stronger than those of the ENO1- cells and the parental cells (P<0.05 or P<0.01). 18H12 antibody could accurately recognize ENO1, which was consistent with the commercial antibody recognition band. 18H12 could significantly inhibit self-renewal ability and invasion ability of PAMC-82 cells (P<0.01). Conclusion: Monoclonal antibody 18H12 can significantly inhibit the self-renewal and invasion of gastric cancer stem cells and is expected to be a candidate antibody drug targeting gastric cancer stem cells.
ABSTRACT
The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal evolution hypothesis, only cancer stem cells can initiate tumor formation, self-renew, and differentiate into various kinds of daughter cells. Because gastric cancer can originate from gastric stem cells and their self-renewal mechanism can be used by gastric cancer stem cells, we review here how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth factor, and bone morphogenetic protein signaling, may regulate the self-renewal and differentiation of gastric stem cells and gastric cancer stem cells. In addition, the precancerous change of the gastric epithelium and the status of isolating gastric cancer stem cells from patients are reviewed.
Subject(s)
Humans , Bone Morphogenetic Proteins , Cell Differentiation , Clonal Evolution , Enteroendocrine Cells , Epidermal Growth Factor , Epithelium , Hedgehogs , Neck , Neoplasm Metastasis , Neoplastic Stem Cells , Nuclear Family , Stem Cells , Stomach , Stomach NeoplasmsABSTRACT
Gastric cancer is one of the most common malignant gastrointestinal tumors with a high mortality in China. However, the pathogenesis of gastric cancer is not clear. Recently, with the development of cancer stem cell research, more and more studies have been focused on the gastric cancer stem cell. In this review, we will discuss the conception and the study status of the gastric cancer stem cells in addition to the treatment for the cancer stem cell.
ABSTRACT
Cancer stem cells are defined as the unique subpopulation in the tumors that possess the abili-ty to initiate tumor growth and sustain self-renewal as well as metastatic potential.Accumulating evidences in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs.In recent years,many cancer stem cells have been found,including leukemia,breast cancer,brain ttunor,liv-er cancer,colon carcinoma,etc.In this review,we will discuss the conception and origin of the gastric cancer stem cells,and their role in the development of multi-drug resistance.