Limited capability of regional lymph nodes to eradicate metastatic cancer cells
Limited capability of regional lymph nodes to eradicate metastatic cancer cells
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DOI：
10.1158/0008-5472.can-04-1182
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发表时间：
2004-11-15
期刊：
影响因子：
11.2
通讯作者：
Hibi, T
中科院分区：
文献类型：
--
作者：
Nagata, H;Arai, T;Hibi, T
淋巴结根除癌症的能力是一个有争议的问题。本研究的目的是确定在淋巴结转移的早期阶段肿瘤生长和宿主抵抗之间的相互作用。在大鼠肠系膜淋巴结中建立转移模型，并在体内观察癌细胞的迁移。取出淋巴结进行组织学分析和细胞因子测量。移行癌细胞最初在边缘窦中被捕获。在最初的增加之后，边缘窦中的癌细胞数量下降，直到接种后48小时。48小时前，髓质内的生发中心和淋巴样细胞增生。ED 3（+）巨噬细胞掺入凋亡的癌细胞，但4天后发生显著的癌症增殖。耗尽巨噬细胞的淋巴结被癌细胞大量侵入。淋巴结内肿瘤坏死因子α和白细胞介素（IL）-1 β分别在1 h和3 h后一过性升高，并分别在ED 3（+）和ED 2（+）巨噬细胞中表达。这些变化之后是IL-2的瞬时增加。干扰素-γ和IL-12在转移的早期阶段没有增加，但在48小时后下降。总之，边缘窦构成了阻止癌细胞通过的机械屏障。区域淋巴结的早期病理表现与癌症患者的生存率提高一致。寄生虫巨噬细胞在淋巴结的瞬时抗转移能力中起作用，并且这些细胞分泌的细胞因子在转移的早期阶段增加。细胞因子诱导的恶化可能是随后癌症增殖的原因。
The capacity of lymph nodes to eradicate cancer is a controversial issue. The purpose of this study was to determine the interplay between tumor growth and host resistance at early stages of lymph node metastasis. A metastasis model was made in the rat mesenteric lymph node, and migration of cancer cells was visualized in vivo. The lymph node was removed for histologic analysis and cytokine measurement. Migrant cancer cells were initially arrested in the marginal sinus. After an initial increase, the number of cancer cells in the marginal sinus declined until 48 hours after inoculation. Germinal centers and lymphoid cells in the medulla proliferated before 48 hours. ED3(+) macrophages incorporated apoptotic cancer cells, but significant cancer proliferation occurred after 4 days. Lymph nodes depleted of macrophages were massively invaded by cancer cells. Tumor necrosis factor alpha and interleukin (IL)-1beta in the nodes transiently increased after 1 hour and 3 hours, respectively, and were expressed in ED3(+) and ED2(+) macrophages, respectively. These changes were followed by a transient increase in IL-2. Interferon-gamma and IL-12 did not increase during the early stages of metastasis, but they decreased after 48 hours. In conclusion, the marginal sinus constitutes a mechanical barrier against cancer cell passage. Early pathological manifestations in the regional lymph node are consistent with those in cancer patients with improved survival. Parasinus macrophages play a role in the transient antimetastatic capability of the node, and cytokines secreted by these cells increased at the early stages of metastasis. Deterioration of cytokine induction may be responsible for subsequent cancer proliferation.