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Glioma invasion: Identification of determinants of invasion using time‐lapse imaging
Author(s) -
Phillips Joanna J.,
Dijkgraaf Gerrit P.,
Huillard Emmanuelle,
Rowitch David H.,
Werb Zena
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.172.3
Subject(s) - glioma , microglia , pathology , tumor microenvironment , blood–brain barrier , biology , confocal microscopy , brain tumor , infiltration (hvac) , cancer research , tumor cells , medicine , neuroscience , immunology , central nervous system , microbiology and biotechnology , inflammation , physics , thermodynamics
Glioblastoma multiforme (GBM) is a malignant glial tumor that is nearly uniformly fatal despite use of current surgical, radio‐ and chemotherapeutic modalities. GBM infiltrate into the surrounding brain, making them highly resistant to treatment. To design improved therapeutics for GBM, we need to understand the factors that drive tumor cell invasion. Using a robust model for glioma we are studying how alterations in the tumor microenvironment influence tumor cell invasion. During tumor development we have identified specific patterns of glioma cell invasion using both immunohistochemistry and ex vivo brain/glioma slice cultures. We monitored the dynamic interaction between fluorescently tagged tumor cells and components of the microenvironment (blood vessels and microglia/macrophages), at various stages of tumor development using four‐color spinning disk confocal microscopy. We determined that tumor cells can invade along blood vessels, and we are examining the role of microglia/macrophages in this mode of invasion. This mechanism of infiltration emphasizes the importance of the perivascular niche, as it may provide crucial factors for brain tumor progenitor cells. By understanding the factors that influence the interaction of tumor cells and blood vessels we hope to elucidate potential new targets for tumor therapy.