Identification of Metaplastic and Pre-Neoplastic Stem/Progenitor Cells
Abstract
Stomach cancer arises within a field of precancerous metaplastic lineages. The present proposal focuses on understanding the earliest stages of gastric carcinogenesis to define therapies that can prevent or reverse pre-cancerous lesions. Two types of metaplasia are observed in the atrophic human stomach: intestinal metaplasia and Spasmolytic Polypeptide (TFF2) Expressing Metaplasia (SPEM). Both of these metaplasias are associated with development of intestinal type cancers in the stomach. We have recently developed a novel mouse model for gastric pre-neoplasia, the Mist1-Kras mouse. In this mouse, tamoxifen treatment induces expression of activated Kras (G12D) in mature chief cells in stomach, which incites a series of metaplastic transitions over the following 4 months including first the evolution of SPEM, followed by the emergence of intestinal metaplasia. We now seek to utilize the Mist1-Kras mouse to provide insights into the factors that lead to the evolution of metaplasia into neoplasia. We hypothesize that discrete populations of pre-neoplastic stem cells exist within metaplastic lesions and represent cancer-initiating cells. We will pursue two specific aims: 1) we will utilize gastric metaplasia organoids derived from Mist1-Kras mice to determine the carcinogenic properties of metaplastic lineages and 2) we will identify putative gastric cancer stem/progenitor cell populations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1124279
Entities
People
- Eunyoung Choi
- James R. Goldenring
- Scott Magness
Organizations
- Vanderbilt University