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Selective ablation of tumor-associated macrophages suppresses metastasis and angiogenesis.

ABSTRACT: 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.

SUBMITTER: Lin Y

PROVIDER: S-EPMC3766435 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Selective ablation of tumor-associated macrophages suppresses metastasis and angiogenesis.

Lin Yingying Y Wei Chongyang C Liu Yuan Y Qiu Yongming Y Liu Cheng C Guo Fang F

Cancer science 20130619 9

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 suppresso ...[more]

PMID: 23691974

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Project description: Not available

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