Tumor-Associated Macrophages Extend Along Lymphatic Flow in the Pre-metastatic Lymph Nodes of Human Gastric Cancer.
BACKGROUND
Tumor-associated macrophages (TAMs) correlate with lymphangiogenesis in primary lesions and with lymph node (LN) metastasis of several cancers. However, the association of TAMs in regional LNs with lymphatic spread of cancer remains unclear. The purpose of this study was to evaluate the distribution of TAMs in draining LNs and the impact of TAMs on the establishment of LN metastasis of gastric cancer.


METHODS
The number and distribution of TAMs in regional LNs that were obtained from 49 patients who underwent radical surgery for gastric cancer at Osaka City University Hospital in 2011 were assessed. TAMs were defined as immunohistochemically CD163 positive cells. The association of the TAM density with lymph node metastasis and the lymphatic drainage route of the stomach were investigated.


RESULTS
A high density of TAMs was significantly associated with pathologically positive lymph nodes and pathological TNM stage. The density of TAMs was increased in LNs with micro metastasis compared with those without metastasis. There was a significant, positive correlation between TAM number and lymphatic vessel density in LNs. In nonmetastatic LNs, TAMs were likely to accumulate in the neighborhood of the primary lesion. In addition, the density of TAMs in distant LNs was significantly increased in patients in whom LN metastasis was observed in perigastric LNs.


CONCLUSIONS
Accumulated TAMs may induce lymphangiogenesis and prepare an environment that facilitates cancer proliferation in LNs. Our findings might provide a conceptual framework for understanding the lymphatic spreading of cancer and for designing future therapeutic strategies for gastric cancer.
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. yukie_05_g@yahoo.co.jp.
Yukie
Y
Go
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. hiroakitan@med.osaka-cu.ac.jp.
Hiroaki
H
Tanaka
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Mao
M
Tokumoto
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Katsunobu
K
Sakurai
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Takahiro
T
Toyokawa
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Naoshi
N
Kubo
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Kazuya
K
Muguruma
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Kiyoshi
K
Maeda
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Masaichi
M
Ohira
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Kosei
K
Hirakawa
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
D014408:Biomarkers, Tumor