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Transdermal drug targeting and functional imaging of tumor blood vessels in the mouse auricle
Author(s) -
Schröder Hannes,
Komljenovic Dorde,
Hecker Markus,
Korff Thomas
Publication year - 2016
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/fj.15-279240
Subject(s) - perfusion , microvessel , angiogenesis , medicine , blood vessel , pathology , transdermal , neovascularization , melanoma , nodule (geology) , blood flow , cancer research , pharmacology , biology , paleontology
Subcutaneously growing tumors are widely utilized to study tumor angiogenesis and the efficacy of antiangiogenic therapies in mice. To additionally assess functional and morphologic alterations of the vasculature in the periphery of a growing tumor, we exploited the easily accessible and hierarchically organized vasculature of the mouse auricle. By site‐specific subcutaneous implantation of a defined preformed mouse B16/F0 melanoma aggregate, a solid tumor nodule developed within 14 d. Growth of the tumor nodule was accompanied by a 4‐fold increase in its perfusion as well as a 2‐ to 4‐fold elevated diameter and perfusion of peripheral blood vessels that had connected to the tumor capillary microvasculature. By trans‐dermal application of the anticancer drug bortezomib, tumor growth was significantly diminished by about 50% without provoking side effects. Moreover, perfusion and tumor microvessel diameter as well as growth and perfusion of arterial or venous blood vessels supplying or draining the tumor microvasculature were decreased under these conditions by up to 80%. Collectively, we observed that the progressive tumor growth is accompanied by the enlargement of supplying and draining extratumoral blood vessels. This process was effectively suppressed by bortezomib, thereby restricting the perfusion capacity of both extra and intratumoral blood vessels.—Schröder, H., Komljenovic, D., Hecker, M., Korff, T. Transdermal drug targeting and functional imaging of tumor blood vessels in the mouse auricle. FASEB J. 30, 923–932 (2016). www.fasebj.org