Reference SummaryChen Q, Life Sci Alliance 2021 Mar;4(3):
Title |
Paneth cell-derived growth factors support tumorigenesis in the small intestine. | ||||
Authors |
Chen Q; Suzuki K; Sifuentes-Dominguez L; Miyata N; Song J; Lopez A; Starokadomskyy P; Gopal P; Dozmorov I; Tan S; Ge B; Burstein E | ||||
Journal |
Life Sci Alliance | ||||
Volume |
4 | ||||
Issue |
3 | ||||
Year |
2021 | ||||
Pages |
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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-alpha subunit. PC depletion in Apc (Min) mice 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. | ||||
Links |
J:305010 – MGI References 33372038 – National Library of Medicine/PubMed |
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Strain Notes
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon adenoma | Intestine - Large Intestine - Colon |
observed - 100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo | Intestine - Large Intestine - Colon adenoma | Intestine - Large Intestine - Colon |
observed |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm1(DTA)Lky | Intestine - Large Intestine - Colon adenoma | Intestine - Large Intestine - Colon |
100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Wnt3tm2Amc/+ | Intestine - Large Intestine - Colon adenoma | Intestine - Large Intestine - Colon |
100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Wnt3tm2Amc | Intestine - Large Intestine - Colon adenoma | Intestine - Large Intestine - Colon |
100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Wnt3tm2Amc | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo | Intestine - Small Intestine - Paneth Cell adenoma | Intestine - Small Intestine - Paneth Cell |
observed |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo | Intestine - Small Intestine - Paneth Cell lesion - neoplastic | Intestine - Small Intestine - Paneth Cell |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
observed - 100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
observed |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm1(DTA)Lky | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
observed - 100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Wnt3tm2Amc/+ | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Wnt3tm2Amc | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
100 |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Wnt3tm2Amc | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine adenoma | Intestine |
observed |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo | Intestine adenoma | Intestine |
observed |
||
| C57BL/6-ApcMin/+ Defa4tm1.1(cre)Fya/+ Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo | Intestine lesion - neoplastic | Intestine |
observed |