The Analysis of Myeloid Monocytic Cells during Tumor Angiogenic Switch

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


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:PC9907-0722
External Project ID:NSC99-2314-B182-038-MY3
Effective start/end date01/08/1031/07/11


  • Hypopharyngeal cancer
  • MRI
  • whole body imaging
  • perfusion-weighted imaging
  • diffusion-weighted imaging


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