B lymphocyte-specific c-myc expression stimulates early and functional expansion of the vasculature and lymphatics during lymphomagenesis

被引:65
作者
Ruddell, A
Mezquita, P
Brandvold, KA
Farr, A
Iritani, BM
机构
[1] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
[2] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA
[3] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA
关键词
D O I
10.1016/S0002-9440(10)63581-X
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Expression of the c-myc proto-oncogene is deregulated in many human cancers. We examined the role of c-Myc in stimulating angiogenesis and lymphangiogenesis in a highly metastatic murine model of Burkitt's lymphoma (Emu-c-myc), where c-Myc is expressed exclusively in B lymphocytes. Immunohistochemical analysis of bone marrow and lymph nodes from young (preneoplastic) Emu-c-myc transgenic mice revealed increased growth of blood vessels, which are functional by dye flow assay. Lymphatic sinuses also increased in size and number within the lymph nodes, as demonstrated by immunostaining for with a lymphatic endothelial marker 10.1.1. The 10.1.1 antibody recognizes VEGFR-2- and VEGFR-3-positive lymphatic sinuses and vessels within lymph nodes, and also recognizes lymphatic vessels in other tissues. Subcutaneously injected dye traveled more efficiently through draining lymph nodes in Emu-c-myc mice, indicating that these hypertrophic lymphatic sinuses increase lymph flow. Purified B lymphocytes and lymphoid tissues from Emu-c-myc mice expressed increased levels of vascular endothelial growth factor (VEGF) by immunohistochemical or immunoblot assays, which could promote blood and lymphatic vessel growth through interaction with VEGFR-2, which is expressed on the endothelium of both vessel types. These results indicate that constitutive c-Myc expression stimulates angiogenesis and lymphangiogenesis, which may promote the rapid growth and metastasis of c-Myc-expressing cancer cells, respectively.
引用
收藏
页码:2233 / 2245
页数:13
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