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

Sun Yat-Sen University, Shengcheng, Guangdong, China
Cancer Research (Impact Factor: 9.28). 12/2006; 66(21):10365-76. DOI: 10.1158/0008-5472.CAN-06-2977
Source: PubMed

ABSTRACT 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.

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    • "These methods have limited sensitivity, because relatively large anatomical sizes are required for reliable detection (Winnard et al. 2008). In addition, current imaging approaches to evaluate lymph node metastasis mainly rely on the size and the shape of the involved lymph node (Qian et al. 2006). However, nodal metastases are often microscopic, so neither computed tomography (CT) nor standard magnetic resonance (MR) imaging can rule them out reliably (Eiber et al. 2010). "
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    • "Human nasopharyngeal carcinoma cell lines CNE-2 and SUNE-1 were maintained in DMEM containing 10% fetal bovine serum and maintained in a humidified atmosphere with 5% CO 2 at 37 °C. S16, a cisplatin-sensitive subclone derived from CNE-2, was isolated by limited dilution as previously described (Qian et al., 2006) and was maintained similarly as the parental CNE-2 cells. "
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    • "Tumor cell intravasation occurs in association with perivascular macrophages [57]. Specialized cells of bone marrow, lymph nodes and lungs take part in formation of the pre-metastatic niche [55] [56] [68]. Cytokines in the hematopoietic microenvironment facilitate leukemic proliferation [69]. "
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