Role of bone marrow-derived stem cells in polyps development in mice with [Apc.sup.Min/+] mutation

We explored the hypothesis that an altered microenvironment (intestinal adenomatous polyp) could modify the differentiation program of bone marrow-derived stem cells (BMSCs), involving them in colon carcinogenesis. Sublethally irradiated 8-week-old female [Apc.sup.Min/+] mice were transplanted with...

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Bibliographic Details
Published in:Stem cells international 2015-01
Main Authors: Barone, Michele, Scavo, Maria Principia, Licinio, Raffaele, Piombino, Michele, De Tullio, Nicola, Mallamaci, Rosanna, Di Leo, Alfredo
Format: Article
Language:English
Subjects:
Bone marrow
Colon cancer
Dysplasia
Genetic aspects
Polyps (Pathology)
Stem cells
Transplantation
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Summary:We explored the hypothesis that an altered microenvironment (intestinal adenomatous polyp) could modify the differentiation program of bone marrow-derived stem cells (BMSCs), involving them in colon carcinogenesis. Sublethally irradiated 8-week-old female [Apc.sup.Min/+] mice were transplanted with bone marrow (BM) cells obtained from either male age-matched [Apc.sup.Min/+] (Apc-Tx-Apc) or wild type (WT) (WT-Tx-Apc) mice. At 4 and 7 weeks after transplantation, BM-derived colonocytes were recognized by colocalization of Y-chromosome and Cdx2 protein (specific colonocyte marker). Polyp number, volume, and grade of dysplasia were not influenced by irradiation/transplantation procedures since they were similar in both untreated female [Apc.sup.Min/+] and Apc-Tx-Apc mice. At 4 and 7 weeks after transplantation, a progressive significant reduction of polyp number and volume was observed in WT-Tx-Apc mice. Moreover, the number of WT-Tx-Apc mice with a high-grade dysplastic polyps significantly decreased as compared to Apc-Tx-Apc mice. Finally, at 4 and 7 weeks after transplantation, WT-Tx-Apc mice showed a progressive significant increase of Y+/Cdx2+ cells in "normal" mucosa, whereas, in the adenomatous tissue, Y+/Cdx2+ cells remained substantially unvaried. Our findings demonstrate that WT BMSCs do not participate in polyp development but rather inhibit their growth. The substitution of genotypically altered colonocytes with Y+/Cdx2+ cells probably contributes to this process.
ISSN:1687-9678
DOI:10.1155/2015/354193