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Science. 2002 Jun 7;296(5574):1883-6. Epub 2002 Apr 25.

Lymphatic metastasis in the absence of functional intratumor lymphatics.

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  • 1E. L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA.


Lymphatic metastasis contributes to mortality from solid tumors. Whether metastasizing cancer cells reach lymph nodes via intratumor lymphatic vessels is unknown. Here, we examine functional lymphatics associated with mouse tumors expressing normal or elevated levels of vascular endothelial growth factor-C (VEGF-C), a molecule that stimulates lymphangiogenesis. Although VEGF-C overexpression increased lymphatic surface area in the tumor margin and lymphatic metastasis, these tumors contained no functional lymphatics, as assessed by four independent functional assays and immunohistochemical staining. These findings suggest that the functional lymphatics in the tumor margin alone are sufficient for lymphatic metastasis and should be targeted therapeutically.

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