Open AccessSelective ablation of tumor‐associated macrophages suppresses metastasis and angiogenesis
Author(s) -
Lin Yingying,
Wei Chongyang,
Liu Yuan,
Qiu Yongming,
Liu Cheng,
Guo Fang
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12202
Subject(s) - prodrug , cancer research , metastasis , angiogenesis , doxorubicin , immune system , extravasation , medicine , chemistry , pharmacology , immunology , chemotherapy , cancer
Tumor‐associated macrophages ( TAM ) play a critical role in promoting tumor development and metastasis. In the present study, we found that legumain, an asparaginyl endopeptidase, was highly expressed on the surface of TAM . A doxorubicin‐based prodrug specifically activated by legumain selectively ablated TAM and resulted in a significant reduction of angiogenic factors and related tumor vessel growth. Treatment with the prodrug also suppressed circulating tumor cells and myeloid immune suppressor Gr‐1+/CD11b+ cells in tumor‐bearing animals. After selective ablation of TAM using the prodrug, tumor growth and metastases were greatly inhibited in murine tumor models. These results indicate that legumain‐activated prodrugs targeting TAM in tumors might represent a novel anticancer strategy.