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Kodama et al. J Cancer Metastasis Treat 2018;4:56 Journal of Cancer
DOI: 10.20517/2394-4722.2018.61 Metastasis and Treatment

Original Article Open Access

Tumor cell invasion from the marginal sinus into
extranodal veins during early-stage lymph node

metastasis can be a starting point for hematogenous
metastasis

Tetsuya Kodama , Shiro Mori 1,2,3 , Masato Nose 4
1,2
1 Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8575, Japan.
2 Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-
8575, Japan.
3 Department of Oral and Maxillofacial Surgery, Tohoku University Hospital, Sendai 980-8575, Japan.
4 Institute for Promotion of Advanced Science and Technology, Ehime University, Matsuyama 790-8577, Japan.
Correspondence to: Prof. Tetsuya Kodama, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba,
Sendai 980-8575, Japan. E-mail: kodama@tohoku.ac.jp

How to cite this article: Kodama T, Mori S, Nose M. Tumor cell invasion from the marginal sinus into extranodal veins during
early-stage lymph node metastasis can be a starting point for hematogenous metastasis. J Cancer Metastasis Treat 2018;4:56.
http://dx.doi.org/10.20517/2394-4722.2018.61

Received: 10 Sep 2018 First Decision: 7 Oct 2018 Revised: 20 Oct 2018 Accepted: 29 Oct 2018 Published: 9 Nov 2018

Science Editor: William Schiemann Copy Editor: Cai-Hong Wang Production Editor: Zhong-Yu Guo

Abstract
Aim: To investigate whether tumor cells in a lymph node (LN) can invade from the marginal sinus into extranodal
veins via vessel branches that communicate with intranodal veins and whether this can be a starting point for
hematogenous metastasis at the early stage of LN metastasis.

Methods: Vascular and lymphatic networks of LNs in MXH10/Mo-lpr/lpr mice were investigated using three-
dimensional micro-computed tomography and histological methods. Flow in the blood vessel networks of LNs
was investigated by fluorescence microscopy. Tumor cells were injected into the subiliac LNs of MXH10/Mo-
lpr/lpr mice to induce metastasis to the proper axillary LNs. Tumor development in the proper axillary LN was
detected using an in vivo bioluminescence imaging system. A two-dimensional image of the proper axillary LN
microvasculature was reconstructed using a contrast-enhanced high-frequency ultrasound system.

Results: Extranodal veins communicated with intranodal veins via branches that penetrated the capsule, and
blood flowed from intranodal veins to extranodal veins. Tumor cells that had metastasized to the marginal sinus
invaded these communicating veins to develop hematogenous metastases.

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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