Limited Capability of Regional Lymph Nodes to Eradicate Metastatic Cancer Cells

Abstract

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 ␣ and interleukin (IL)-1␤ 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-␥ 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.

Auxiliary diagnosis of lymph node metastasis in early gastric cancer using quantitative evaluation of sentinel node radioactivity

“…Lymphangiogenesis in regional lymph nodes plays an early role in spreading tumor cells though the lymphatic system to distant organs in gastric cancer. Nagata et al observed morphological changes in lymph nodes during the establishment of lymph node metastasis using a rat mesenteric SN model [26]. Watanabe et al reported that intranodal lymphatic vessel density was significantly correlated with the size of the metastasis [27].…”

HMGB1 Attenuates Anti-Metastatic Defense of the Lymph Nodes in Colorectal Cancer

“…Sinus macrophages mediate the phagocytosis of cancer cells attached to the sinus wall and destroy them in order to inhibit their metastasis [26,27] . Sinus macrophages are also a part of an anti-cancer cytokine network involving TNF-␣ and IL-1 ␤ [28,29] . The genes expressed in the sinus macrophages in the lymph nodes and liver were distinct from those expressed in the splenic sinus macrophages, e.g.…”

In Situ Lymph Dynamic Characterization through Lymph Nodes in Rabbit Hind Leg: Special Reference to Nodal Inflammation

“…Nagata et al (2004) [7] showed that macrophages beneath the marginal sinus form the first line of defense against cancer cell invasion. They also demonstrated that a variety of cytokines is secreted in the LNs of tumor-bearing animals and described that it is possible to modify the metastatic process by the artificial manipulation of the cytokine environment.…”