@article{9aa22e2e7fd94dddb24ddb288dd3325e,
title = "Intravital imaging of vascular anomalies and extracellular matrix remodeling in orthotopic pancreatic tumors",
abstract = "Pancreatic cancers, both adenocarcinomas and endocrine tumors are characterized by varying levels of aberrant angiogenesis and fibrotic microenvironment. The difficulty to deliver drugs and treat the disease has been attributed in part to the vascular architecture and tissue/ECM density. Here we present longitudinal three-dimensional intravital imaging of vascular and tumor microenvironment remodeling in spontaneous transgenic tumors (RIP1-Tag2 insulinomas) and orthotopically injected tumors (KPC adenocarcinomas). Analysis of the data acquired in insulinomas revealed major differences in tumor blood vessel branching, fraction volume, number of branch points segments, vessel straightness and length compared to the normal tissue. The aggressive adenocarcinoma presented widespread peritumoral vascular remodeling and heterogeneous vascular distribution. Longitudinal imaging was used to acquire sequential vascular remodeling data during tumor progression. This work demonstrates the potential for using a pancreatic intravital imaging window for direct visualization of the tumor heterogenic microenvironments during tumor progression.",
keywords = "adenocarcinoma, insulinoma, pancreatic cancer, two-photon microscopy, vasculogenesis",
author = "Filip Bochner and Vishnu Mohan and Assaf Zinger and Ofra Golani and Avi Schroeder and Irit Sagi and Michal Neeman",
note = "Funding Information: We would like to express our gratitude to Dr Vyacheslav Kalchenko for help with the 2P and intravital microscopy. Our thanks to Dr Ori Brenner for pathological assessment of tissues and Dr Inna Solomonov for support with experiment planning and manuscript writing. We acknowledge Prof Ziv Gil and Prof Johanna A. Joyce for providing the animal models. We thank Marina Cohen for help with histological staining. This work was supported in part by the European Commission Horizon 2020 research and innovation programme (grant agreement No. 801126; to I.S.); European Research Council (ERC) under the European Commission Horizon 2020 research and innovation programme (grant agreement No. 695437; to I.S.); Israel Science Foundation (1800/19; to I.S.), the USA‐Israel Binational Science Foundation (712506‐01; to I.S.); Israel Science Foundation grants 326/14 (to M.N.); The Benoziyo Endowment Fund for the Advancement of Science (to M.N.); and by the Thompson Family Foundation grant “Targeting Pancreas Cancer” (to I.S. and M.N.). Irit Sagi is the Incumbent of the Maurizio Pontecorvo Professorial Chair. Michal Neeman is the incumbent of the Helen and Morris Mauerberger Professorial Chair in Biological Sciences. Funding Information: We would like to express our gratitude to Dr Vyacheslav Kalchenko for help with the 2P and intravital microscopy. Our thanks to Dr Ori Brenner for pathological assessment of tissues and Dr Inna Solomonov for support with experiment planning and manuscript writing. We acknowledge Prof Ziv Gil and Prof Johanna A. Joyce for providing the animal models. We thank Marina Cohen for help with histological staining. This work was supported in part by the European Commission Horizon 2020 research and innovation programme (grant agreement No. 801126; to I.S.); European Research Council (ERC) under the European Commission Horizon 2020 research and innovation programme (grant agreement No. 695437; to I.S.); Israel Science Foundation (1800/19; to I.S.), the USA-Israel Binational Science Foundation (712506-01; to I.S.); Israel Science Foundation grants 326/14 (to M.N.); The Benoziyo Endowment Fund for the Advancement of Science (to M.N.); and by the Thompson Family Foundation grant ?Targeting Pancreas Cancer? (to I.S. and M.N.). Irit Sagi is the Incumbent of the Maurizio Pontecorvo Professorial Chair. Michal Neeman is the incumbent of the Helen and Morris Mauerberger Professorial Chair in Biological Sciences. Publisher Copyright: {\textcopyright} 2019 UICC",
year = "2020",
month = apr,
day = "15",
doi = "10.1002/ijc.32759",
language = "English (US)",
volume = "146",
pages = "2209--2217",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley",
number = "8",
}