Preparing the soil : The primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells

Sentinel lymph node (SLN) metastasis is the first step in the spreading of cancer in many malignancies. Tumor-reactive lymphadenopathy in SLNs has been observed for decades, but alterations of the lymphatic channels and vasculature in these nodes before the arrival of metastatic tumor cells remain u...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006-11, Vol.66 (21), p.10365-10376
Main Authors: QIAN, Chao-Nan, BERGHUIS, Bree, JINDONG CHEN, RESAU, James H, BIN TEAN TEH, TSARFATY, Galia, BRUCH, Marybeth, KORT, Eric J, DITLEV, Jon, TSARFATY, Ilan, HUDSON, Eric, JACKSON, David G, PETILLO, David
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation
Endothelial Cells - cytology
Endotoxins - toxicity
Female
Humans
Lymph Nodes - blood supply
Lymphangiogenesis
Lymphatic Metastasis
Medical sciences
Mice
Mice, Inbred BALB C
Nasopharyngeal Neoplasms - blood supply
Nasopharyngeal Neoplasms - pathology
Pharmacology. Drug treatments
Tumors
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Summary:Sentinel lymph node (SLN) metastasis is the first step in the spreading of cancer in many malignancies. Tumor-reactive lymphadenopathy in SLNs has been observed for decades, but alterations of the lymphatic channels and vasculature in these nodes before the arrival of metastatic tumor cells remain unexplored. Using animal models, we show here that, before the establishment of metastasis in the SLN, there are reorganizations of the lymphatic channels and the vasculature. The node becomes a functional blood vessel-enriched and lymph vessel/sinus-enriched organ before metastasis. The enlargement of the lymph sinuses is correlated with the primary tumor weight. The newly emerged functional blood vessels develop from high endothelial venules (HEV), in which the proliferation rate of the endothelial cells is also significantly increased. Similar alterations of the HEVs are also characterized in the axillary lymph nodes from human breast cancer patients without the evidence of metastasis. These findings support the hypothesis that modification of the microenvironment for a secondary tumor (i.e., vasculature reorganization in the SLN) can be initiated by a primary tumor before and independent of the physical presence of metastatic cancer cells.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-06-2977