TY - JOUR
T1 - Distinctive features of angiogenesis and lymphangiogenesis determine their functionality during de novo tumor development
AU - Eichten, Alexandra
AU - Hyun, William C.
AU - Coussens, Lisa M.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Blood and lymphatic vasculature are essential components of all organs, responsible for maintaining organ fluid dynamics and tissue homeostasis. Although both vessel systems are composed of similar lineages of endothelial cells whose crude functions include fluid and cell transport, each system also possesses distinctive physiologic properties, enabling their distinctive functions in tissues. The role of hematogenous vasculature and development of angiogenic blood vessels during cancer development is well established; however, the role of lymphangiogenesis and structural/functional alterations occurring within lymphatic vessels during cancer development are incompletely understood. To assess premalignant versus malignant alterations in blood and lymphatic vasculature associated with squamous epithelial skin carcinogenesis, we assessed architectural and functional features of both vascular systems using a mouse model of de novo carcinoma development. We report that, as vasculature acquires angiogenic and/or lymphangiogenic properties, angiogenic blood vessels become leaky in premalignant tissue and at peripheries of carcinomas, where enlarged lymphatic capillaries efficiently drain increased tissue fluid, thereby maintaining tissue hemodynamics. In contrast, central regions of carcinomas exhibit elevated tissue fluid levels, compressed lymphatic lumina, and decreased vascular leakage, thus indicating impaired hemodynamics within solid tumors. Together, these data support the notion that therapeutic delivery of anticancer agents is best realized in premalignant tissues and/or at the peripheries of solid tumors where hemodynamic forces support drug delivery. Strategies to normalize intratumoral hemodynamics would therefore enhance therapeutic delivery to otherwise poorly accessible central regions of solid tumors.
AB - Blood and lymphatic vasculature are essential components of all organs, responsible for maintaining organ fluid dynamics and tissue homeostasis. Although both vessel systems are composed of similar lineages of endothelial cells whose crude functions include fluid and cell transport, each system also possesses distinctive physiologic properties, enabling their distinctive functions in tissues. The role of hematogenous vasculature and development of angiogenic blood vessels during cancer development is well established; however, the role of lymphangiogenesis and structural/functional alterations occurring within lymphatic vessels during cancer development are incompletely understood. To assess premalignant versus malignant alterations in blood and lymphatic vasculature associated with squamous epithelial skin carcinogenesis, we assessed architectural and functional features of both vascular systems using a mouse model of de novo carcinoma development. We report that, as vasculature acquires angiogenic and/or lymphangiogenic properties, angiogenic blood vessels become leaky in premalignant tissue and at peripheries of carcinomas, where enlarged lymphatic capillaries efficiently drain increased tissue fluid, thereby maintaining tissue hemodynamics. In contrast, central regions of carcinomas exhibit elevated tissue fluid levels, compressed lymphatic lumina, and decreased vascular leakage, thus indicating impaired hemodynamics within solid tumors. Together, these data support the notion that therapeutic delivery of anticancer agents is best realized in premalignant tissues and/or at the peripheries of solid tumors where hemodynamic forces support drug delivery. Strategies to normalize intratumoral hemodynamics would therefore enhance therapeutic delivery to otherwise poorly accessible central regions of solid tumors.
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U2 - 10.1158/0008-5472.CAN-06-4676
DO - 10.1158/0008-5472.CAN-06-4676
M3 - Article
C2 - 17545601
AN - SCOPUS:34347270589
SN - 0008-5472
VL - 67
SP - 5211
EP - 5220
JO - Cancer Research
JF - Cancer Research
IS - 11
ER -