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Lymphatic vessel density and function in experimental bladder cancer.

Marcia R Saban1, Rheal Towner, Nataliya Smith

  • 1Department of Physiology, College of Medicine, Oklahoma University Health Sciences Center (OUHSC), Oklahoma City, OK 73104, USA. marcia-saban@ouhsc.edu

BMC Cancer
|December 1, 2007
PubMed
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This study visualizes bladder lymphatics in a new mouse model, revealing increased lymphatic vessel density and altered function during cancer progression. These findings highlight lymphangiogenesis

Area of Science:

  • Oncology
  • Vascular Biology
  • Biomedical Imaging

Background:

  • The lymphatic system is crucial for fluid balance and immune surveillance, draining the tumor microenvironment.
  • Lymphangiogenesis, the formation of new lymphatic vessels, is associated with cancer and inflammation.
  • The role of bladder lymphatic vessels in bladder cancer development and progression remains largely unexplored.

Purpose of the Study:

  • To develop and utilize a novel transgenic mouse model for visualizing and assessing bladder lymphatic vessels during cancer progression.
  • To investigate changes in lymphatic vessel density (LVD) and lymphatic vessel function (LVF) in the context of bladder cancer.
  • To evaluate the utility of a dual-contrast agent for magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) in studying lymphatic dynamics.

Related Experiment Videos

Main Methods:

  • Generation of a double transgenic mouse model (SV40-lacZ) combining bladder cancer induction with a lymphatic endothelial cell reporter.
  • Assessment of LVD using fluorescent immunohistochemistry (IHC) with LYVE-1 antibody on bladder whole mounts and sections.
  • Evaluation of LVF using in vivo MRI and NIRF imaging with a dual-contrast agent (Gd-Cy5.5) to track macromolecular fluid flow.

Main Results:

  • The SV40-lacZ mouse model successfully developed bladder cancer and allowed for lymphatic visualization.
  • A significant increase in LVD was observed, correlating with bladder cancer progression, indicating cancer-induced lymphangiogenesis.
  • MRI detected tumors early, and lymphangiography revealed potential reductions in lymphatic flow within the tumor area, confirmed by NIRF studies.

Conclusions:

  • The SV40-lacZ mouse model provides a valuable tool for real-time in vivo visualization of lymphatic activity during bladder cancer.
  • The dual-contrast agent Gd-Cy5.5 enables quantitative assessment of fluid transport through the interstitial-lymphatic system.
  • The study supports a role for lymphangiogenesis in bladder cancer progression and opens avenues for further research into lymphatic dynamics.