Abstract 178P
Background
Rapidly proliferating stomach stem cells have been predicted to be located at the isthmus of both corpus and antrum. We recently identified such stem cells by using 270 bp Runx1 enhancer element, eR1 (Gastroenterol, 2017). In addition, eR1 also marked small number of fully differentiated chief cells in the corpus. We investigated whether chief cells have stem cell activity and can be an origin of gastric cancer, particularly because there are disagreements among the researchers.
Methods
We generated knock-in mice of pepsinogen C-CreERT2 and crossed them with Rosa26-EYFP mice or pepsinogen A-CreERT2 and crossed them with Rosa26-tdTomato mice for lineage tracing. PGC-CreERT2 mice were also crossed with K-rasG12D/+, Trp53flox/flox and Apcflox/floxmice for carcinogenesis model. Those mice were injected with Tamoxifen 2 mg alternate days for 6 timesto activate Cre recombinase in the chief cells.
Results
By activating Cre recombinase, we showed that relatively small number of chief cells was retro-differentiated into neck, parietal, pit and enteroendocrinecells suggesting that chief cells underwent differentiation in exact reverse order to make a complete gland unit. When K-rasG12Dwas activated by pepsinogen C-CreERT2, induction of metaplasia was observed. Addition of p53 knockout with K-rasG12Dinto chief cells showed increasing number of glands with metaplasia. Furthermore, addition of APC knockout combination with K-rasG12Dand p53f/fshowed invasive intestinal type gastric cancer in the corpus. These results suggest that at least small subfraction of chief cell have stem cell activity and potential to give rise to gastric cancer. Recently, new entity of gastric adenocarcinoma has been proposed which called Gastric adenocarcinoma of fundic gland type (chief cell predominant type). We might have showed those type of gastric carcinogenesis.
Conclusions
Chief cell in stomach have stem cell activity and potential to develop gastric cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Singapore Gastric Cancer Consortium.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
9P - XRCC1 Arg194Trp, Palb2 T1100T (3300T>G), HMMR V353A, TNF aG308A polymorphisms as diagnostic and prognostic markers of breast cancer in the Kyrgyz ethnic group
Presenter: Aigul Semetei kyzy
Session: Poster display session
Resources:
Abstract
232P - Early Results from the Phase I Study of SY-1365, a Potent and Selective CDK7 inhibitor, in Patients with Ovarian Cancer and Advanced Solid Tumors
Presenter: Debra Richardson
Session: Poster display session
Resources:
Abstract
382P - Drug metabolizing enzymes pharmacogenomic: Biomarkers for improved chemotherapy in head and neck cancer squamous cell carcinoma
Presenter: Sunishtha Bhatia
Session: Poster display session
Resources:
Abstract
401P - Women in oncology: Alarming figures from India
Presenter: Sharada Mailankody
Session: Poster display session
Resources:
Abstract
416P - Multidisciplinary management of sarcomas of the head and neck: An institutional experience
Presenter: Kavitha Jain
Session: Poster display session
Resources:
Abstract
523P - Co-morbilities and survival of patients initially diagnosed with extensive-stage small cell lung cancer: Impact of hypertension, diabetes and chronic hepatitis B viral infection
Presenter: Weigang Xiu
Session: Poster display session
Resources:
Abstract
529P - Osimertinib for patients with EGFR-mutant advanced NSCLC and asymptomatic brain metastases: An open-label, two-arm, phase II study
Presenter: Roni Gillis
Session: Poster display session
Resources:
Abstract