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Am J Pathol. 2007 Feb;170(2):774-86.

Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis.

Author information

1
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Department of Comparative Medicine, University of Washington, 1100 Fairview Ave. N., MS-C2-023, P.O. Box 19024, Seattle, WA 98109, USA. aruddell@fhcrc.org.

Abstract

Lymphangiogenesis is associated with human and murine cancer metastasis, suggesting that lymphatic vessels are important for tumor dissemination. Lymphatic vessel alterations were examined using B16-F10 melanoma cells implanted in syngeneic C57Bl/6 mice, which form tumors metastasizing to draining lymph nodes and subsequently to the lungs. Footpad tumors showed no lymphatic or blood vessel growth; however, the tumor-draining popliteal lymph node featured greatly increased lymphatic sinuses. Lymph node lymphangiogenesis began before melanoma cells reached draining lymph nodes, indicating that primary tumors induce these alterations at a distance. Lymph flow imaging revealed that nanoparticle transit was greatly increased through tumor-draining relative to nondraining lymph nodes. Lymph node lymphatic sinuses and lymph flow were increased in mice implanted with unmarked or with foreign antigen-expressing melanomas, indicating that these effects are not due to foreign antigen expression. However, tumor-derived immune signaling could promote lymph node alterations, as macrophages infiltrated footpad tumors, whereas lymphocytes accumulated in tumor-draining lymph nodes. B lymphocytes are required for lymphangiogenesis and increased lymph flow through tumor-draining lymph nodes, as these alterations were not observed in mice deficient for B cells. Lymph node lymphangiogenesis and increased lymph flow through tumor-draining lymph nodes may actively promote metastasis via the lymphatics.

PMID:
17255343
PMCID:
PMC1851877
DOI:
10.2353/ajpath.2007.060761
[Indexed for MEDLINE]
Free PMC Article

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