|dc.contributor.author||Le Brenne, Arielle||
|dc.identifier.citation||Le Brenne, A. 2014. Contribution of Bone Marrow Derived Cells to Four Mouse Models of Gastrointestinal Tumourigenesis. Queen Mary University of London.||en_US
|dc.description.abstract||Introduction: Houghton and colleagues (2004) demonstrated bone marrow
derived cells (BMDCs) to be the origin of epithelial cells in pre-‐‑invasive and
malignant gastric tumours in Helicobacter felis infected mice. However, this has
yet to be replicated in any other experimental scenario.
Methods: To clarify the significance of Houghton’s observation we examined
four mouse models of gastrointestinal tumourigenesis: the Tff1-‐‑/-‐‑ mouse model
of inflammatory gastric adenocarcinoma, the ApcMin/+ and Apc1322T mouse models
of familial adenomatous polyposis, and the Il10-‐‑/-‐‑ mouse model of colitis-‐‑
associated colorectal adenocarcinoma, employing sex-‐‑mismatched bone
marrow (BM) transplantation (male BM to female recipients) followed by the
identification of BMDCs in tissues using Y-‐‑chromosome in situ hybridisation
(ISH) detection and immunohistochemical phenotyping of cells. To investigate
the mechanism for BMDC recruitment into tissues, osteopontin (Opn) mRNA
isotopic ISH was employed.
Results: In four mouse models there was not a single instance of a gastric
gland or intestinal crypt with a patch of clonal Y-‐‑chromosome positive (Y+)
cells. Y+ cells in the epithelium were very rare and were mostly positive for
several markers of immune cells. In contrast, Y+ cells were frequently observed
in the stroma. Quantification of BMD-‐‑myofibroblasts demonstrated increased
recruitment into larger Apc1322T mouse tumours and desmoplastic reaction sites
in Tff1-‐‑/-‐‑ mouse tumours, but not into inflamed non-‐‑fibrotic tissues. Similarly,
Opn mRNA expression was unaffected by inflammation but increased with
tumour burden and in desmoplastic reaction sites. In the desmoplastic reaction
sites of Tff1-‐‑/-‐‑ mouse tumours, increased osteopontin mRNA expression
correlated with increased BMD-‐‑myofibroblasts, therefore suggesting some
chemoattraction was occurring.
Conclusions: In four mouse models of gastrointestinal tumourigenesis BMDCs
were not a source of reparative, pre-‐‑cancerous, or malignant epithelial cells.
Analysis of BM contribution in the stroma demonstrated that BMD-‐‑
myofibroblast engraftment is driven by increased tumour burden and fibrosis.
In addition, the increased presence of BMD-‐‑myofibroblasts at desmoplastic
reaction sites of Tff1-‐‑/-‐‑ mouse tumours correlated with increased Opn mRNA
expression, indicating that osteopontin may act as chemoattractant in
|dc.description.sponsorship||Saint Bartholomew'ʹs and
The Royal London Charitable Foundation||en_US
|dc.publisher||Queen Mary University of London||en_US
|dc.title||Contribution of Bone Marrow Derived Cells to Four Mouse Models of Gastrointestinal Tumourigenesis.||en_US
|dc.rights.holder||The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author||