Macrophage Infiltration Predicts a Poor Prognosis for Human Ewing Sarcoma

被引：131

作者：

Fujiwara, Toshifumi ^{[1
]}

Fukushi, Jun-ichi ^{[1
]}

Yamamoto, Shunsaku ^{[1
]}

Matsumoto, Yoshihiro ^{[1
]}

Setsu, Nokitaka ^{[2
]}

Oda, Yoshinao ^{[2
]}

Yamada, Hisakata ^{[4
]}

Okada, Seiji ^{[3
]}

Watari, Kosuke ^{[5
]}

Ono, Mayumi ^{[5
]}

Kuwano, Michihiko ^{[6
]}

Kamura, Satoshi ^{[1
]}

Iida, Keiichiro ^{[1
]}

Okada, Yuko ^{[1
]}

Koga, Mihoko ^{[1
]}

Iwamoto, Yukihide ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Orthopaed Surg, Fukuoka 8128582, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Fukuoka 8128582, Japan

[3] Kyushu Univ, Grad Sch Med Sci, Adv Med Initiat, Fukuoka 8128582, Japan

[4] Kyushu Univ, Grad Sch Med Sci, Div Host Def, Fukuoka 8128582, Japan

[5] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Pharmaceut Oncol, Fukuoka 8128582, Japan

[6] Kyushu Univ, Grad Sch Pharmaceut Sci, Lab Mol Canc Biol, Dept Pharmaceut, Fukuoka 8128582, Japan

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2011年 / 179卷 / 03期

基金：

日本学术振兴会;

关键词：

TUMOR-ASSOCIATED MACROPHAGES; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BREAST-CANCER METASTASIS; GROWTH-FACTOR; POSSIBLE INVOLVEMENT; OSTEOCLAST FORMATION; CELL INFILTRATION; IN-VITRO; ANGIOGENESIS; EXPRESSION;

D O I：

10.1016/j.ajpath.2011.05.034

中图分类号：

R36 [病理学];

学科分类号：

100103 [病原生物学];

摘要：

Ewing sarcoma primitive neuroectodermal tumor (EWS) is associated with the most unfavorable prognosis of all primary musculoskeletal tumors. The objective of the present study was to investigate whether tumor-associated macrophages (TAMs) affect the development of EWS. TAMs were isolated from mouse xenografts using CD11b magnetic beads and examined for their cytokine expression and osteoclastic differentiation. To evaluate the role of TAMs in xenograft formation, liposome-encapsulated clodronate was used to deplete TAMs in mice. Macrophage infiltration and tumor microvascular density were histologically evaluated in 41 patients with EWS, and association with prognosis was examined using Kaplan-Meier survival analysis. In mouse EWS xenografts, TAMs expressed higher concentrations of cytokines including interleukin-6, keratinocyte-derived chemokine, and monocyte chemotactic protein-1. TAMs were more capable than normal monocytes of differentiating into tartrate-resistant acid phosphatase positive giant cells. Depleting macrophages using liposome-encapsulated clodronate significantly inhibited development of EWS xenografts. In human EWS samples, higher levels of CD68-positive macrophages were associated with poorer overall survival. In addition, enhanced vascularity, increase in the amount of C-reactive protein, and higher white blood cell counts were also associated with poor prognosis and macrophage infiltration. TAMs seem to enhance the progression of EWS by stimulating both angiogenesis and osteoclastogenesis. Further investigation of the behavior of TAMs may lead to development of biologically targeted therapies for EWS. (Am J Pathol 2011, 170:1157-1170; 10.1016/j.ajpath.2011.05.034)

引用

页码：1157 / 1170

页数：14

共 75 条

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