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Lymphatic Metastasis in the Absence of Functional Intratumor Lymphatics
Timothy P. Padera,1Ananth Kadambi,1*Emmanuelle di Tomaso,1Carla Mouta Carreira,1Edward B. Brown,1Yves Boucher,1Noah C. Choi,1Douglas Mathisen,2John Wain,2Eugene J. Mark,3Lance L. Munn,1Rakesh K. Jain1
Lymphatic metastasis contributes to mortality from solid tumors.
Whether metastasizing cancer cells reach lymph nodes viaintratumor
lymphatic vessels is unknown. Here, we examine functionallymphatics
associated with mouse tumors expressing normal or elevatedlevels of
vascular endothelial growth factor-C (VEGF-C), a
moleculethat stimulates lymphangiogenesis. Although VEGF-C
overexpressionincreased lymphatic surface area in the tumor margin and
lymphaticmetastasis, these tumors contained no functional lymphatics,
asassessed by four independent functional assays and
immunohistochemicalstaining. These findings suggest that the
functional lymphaticsin the tumor margin alone are sufficient for
lymphatic metastasisand should be targeted therapeutically.
1 E. L. Steele Laboratory, Department of
Radiation Oncology,
2 Department of Surgery,
3 Department of Pathology, Massachusetts General
Hospital, Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA.
*
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, ME04074, USA.
To whom correspondence should be addressed. E-mail:
jain{at}steele.mgh.harvard.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Jeffrey E. Gershenwald and Isaiah J. Fidler (7 June 2002) Science296 (5574), 1811.
[DOI: 10.1126/science.10731318] |Summary »|Full Text »|PDF »
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