Lymphatic Metastasis in the Absence of Functional Intratumor Lymphatics

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Science  07 Jun 2002:
Vol. 296, Issue 5574, pp. 1883-1886
DOI: 10.1126/science.1071420

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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.

  • * Present address: Comprehensive Cancer Center, University of California-San Francisco, 2340 Sutter Street, N461, San Francisco, CA 94143-0808, USA.

  • Present address: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.

  • To whom correspondence should be addressed. E-mail: jain{at}

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