Project Details
Abstract
Angiogenic switch is the key step for tumor exponential growth. Understanding of the
mechanism of angiogenic switch may facilitate the development of novel early
biomarkers, diagnosis and therapeutic targeting. Angiogenic switch is mainly induced by
infiltrating bone marrow-derived cells (BMDC). BMDC is a heterogeneous population
with cells primarily expressing monocytic markers called myeloid monocytic cells
(MMC). How MMC specifically promotes angiogenic switch is unclear. Previously, we
have reported a tumor model in immunocompetent mice through the EBV oncogene
N-LMP1 (a Taiwan isolate)-mediated oncogenesis. By using dynamic contract-enhanced
magnetic resonance imaging (DCE-MRI), we have further identified a seven-day period
of angiogenic switch in the model based on the change of vascular permeability index,
Ktrans, before exponential progression. In this three-year proposal, we focus on the
analysis of the role of MMC plays in the 7-day period. The requirement of MMC for
angiogenic switch will be firstly examined by in vivo depletion of MMC before tumor
induction, and followed by monitoring its influence upon Ktrans and tumor volume. As
we postulate that the induction of angiogenic switch may sequentially involve different
subsets of MMC, our second goal is to identify the rhythm of active MMC subsets in the
infiltration during the period by flow cytometry. Finally, cellular MRI will be applied by
intravenous injection of superparamagnetic iron oxide (SPIO) nanoparticles to in vivo
label the MMC to understand the relationship of MMC localization and angiogenic
microenvironment with new tumor mass formation before during and after angiogenic
switch with the aid of immunohistochemical validation.
The specific aims of the three-year project are as follows:
1. To analyze the role of MMC during the angiogenic switch by in vivo depletion of
MMC and assessment of its influence upon Ktrans and tumor volume by DCE-MRI
2. To identify the MMC subsets active during angiogenic switch by flow cytometry
3. To examine the relationship of MMC localization, microenvironment and the
pattern of tumor expansion by cellular MRI technology and
immunohistochemistry
Project IDs
Project ID:PC10001-1126
External Project ID:NSC99-2314-B182-038-MY3
External Project ID:NSC99-2314-B182-038-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/11 → 31/07/12 |
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