Back to Search
Start Over
Selective ablation of tumor-associated macrophages suppresses metastasis and angiogenesis.
- Source :
-
Cancer science [Cancer Sci] 2013 Sep; Vol. 104 (9), pp. 1217-25. Date of Electronic Publication: 2013 Jun 19. - Publication Year :
- 2013
-
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.<br /> (© 2013 Japanese Cancer Association.)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Cell Line, Tumor
Cysteine Endopeptidases biosynthesis
Cysteine Endopeptidases genetics
Cysteine Endopeptidases metabolism
Disease Progression
Doxorubicin analogs & derivatives
Doxorubicin pharmacology
Female
Humans
Macrophages enzymology
Macrophages metabolism
Male
Mice
Mice, Inbred BALB C
Myeloid Cells drug effects
Myeloid Cells metabolism
Myeloid Cells pathology
Neoplasm Metastasis
Neoplasms drug therapy
Neoplasms metabolism
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic genetics
Neovascularization, Pathologic metabolism
Oligopeptides pharmacology
Xenograft Model Antitumor Assays
Macrophages pathology
Neoplasms blood supply
Neoplasms pathology
Neovascularization, Pathologic pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 104
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 23691974
- Full Text :
- https://doi.org/10.1111/cas.12202