The WNT5A Agonist Foxy5 Reduces the Number of Colonic Cancer Stem Cells in a Xenograft Mouse Model of Human Colonic Cancer

Osman, JaninaLund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups (författare)

BACKGROUND: The wingless-type mammary tumour virus integration site 5A (WNT5A) agonist Foxy5 was shown in vitro to affect intracellular signalling implicated in the regulation of colonic cancer stem cells (CSCs). MATERIALS AND METHODS: In order to study whether Foxy5 can modulate CSCs, either HT-29 or Caco-2 human colonic cancer cells, both lacking endogenous WNT5A expression, were inoculated subcutaneously into nude mice. RESULTS: Foxy5 reduced the expression of the stem-cell marker aldehyde dehydrogenase and, interestingly, the specific colon CSC marker double cortin-like kinase 1. Foxy5 also reduced active β-catenin and the expression of its downstream target Achaete Scute complex homolog 2, a CSC-preserving transcription factor. Foxy5 also reduced cyclo-oxygenase 2 expression, responsible for the formation of the CSC-promoting prostaglandin E2 (PGE2), but increased that of 15-hydroxyprostaglandin dehydrogenase expression, a PGE2-degrading enzyme. Accordingly, Foxy5 impairs both β-catenin and PGE2 signalling, both of which have been implicated in promoting the niche of colonic CSCs. CONCLUSION: Our data suggest that Foxy5 can complement the traditional adjuvant chemotherapeutic treatment to which CSCs are resistant.

Bellamkonda, KishanLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-kbl (författare)
Liu, QingLund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups(Swepub:lu)kir-qli (författare)
Andersson, TommyLund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups(Swepub:lu)expp-tan (författare)
Sjölander, AnitaLund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups(Swepub:lu)expp-asj (författare)
Cellpatologi, MalmöForskargrupper vid Lunds universitet (creator_code:org_t)

Ingår i:Anticancer research: Anticancer Research USA Inc.39:4, s. 1719-17281791-75300250-7005

Av författaren/redakt...: Osman, Janina; Bellamkonda, Kis ...; Liu, Qing; Andersson, Tommy; Sjölander, Anita

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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