Paneth cell-derived growth factors support tumorigenesis in the small intestine

Qing Chen, Kohei Suzuki, Luis Sifuentes-Dominguez, Naoteru Miyata, Jie Song, Adam Lopez, Petro Starokadomskyy, Purva Gopal, Igor Dozmorov, Shuai Tan, Bujun Ge, Ezra Burstein

Research output: Contribution to journalArticlepeer-review

Abstract

Paneth cells (PCs) are small intestinal epithelial cells that secrete antimicrobial peptides and growth factors, such as Wnt ligands. Intriguingly, the context in which PC-derived Wnt secretion is relevant in vivo remains unknown as intestinal epithelial ablation of Wnt does not affect homeostatic proliferation or restitution after irradiation injury. Considering the importance of growth factors in tumor development, we explored here the role of PCs in intestinal carcinogenesis using a genetic model of PC depletion through conditional expression of diphtheria toxin-a subunit. PC depletion in ApcMinmice impaired adenoma development in the small intestine and led to decreased Wnt3 expression in small bowel adenomas. To determine if PC-derived Wnt3 was required for adenoma development, we examined tumor formation after PC-specific ablation of Wnt3. We found that this was sufficient to decrease small intestinal adenoma formation; moreover, organoids derived from these tumors displayed slower growth capacity. Overall, we report that PC-derived Wnt3 is required to sustain early tumorigenesis in the small bowel and identify a clear role for PC-derived Wnt production in intestinal pathology.

Original languageEnglish (US)
Article numbere202000934
JournalLife Science Alliance
Volume4
Issue number3
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

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