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Polarization of tumor-associated macrophage is associated with tumor vascular normalization by endostatin
1Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
Background:
Vascular normalization is an emerging concept in cancer treatment, but its precise mechanisms are not completely understood. The polarization of tumor-associated macrophages (TAMs) is important in tumor angiogenesis and metastasis. However, little is known about the effect of anti-angiogenic agents on the polarization of tumor-associated macrophages. Therefore, we explore the changes of TAMs polarization in the development of tumor vascular normalization induced by endostatin.
Methods:
A murine xenograft model of lung cancer was treated with endostatin for 10 days. The morphology and function of tumor vasculature was examined using various techniques. Flow cytometry was carried out to assess the TAMs, and immunofluorescence was used to examine Tie-2-expressing monocytes (TEMs) in tumors. Levels of the histidine-rich glycoprotein (HRG) in tumors were measured by immunohistochemistry and Western blot.
Results:
Tumor vessels became more normal and mature on day six in the endostatin-treated mice. During vascular normalization, the number of M2-like TAMs and TEMs in the tumors was significantly reduced, whereas the number of M1-like TAMs showed an increase on day six after endostatin treatment, although the latter was not statistically significant. The HRG in the tumors accumulated at an early stage after endostatin administration.
Conclusions:
The polarization of TAMs is associated with tumor vascular normalization induced by endostatin. These observations may be useful in the exploration of new strategies for anti-angiogenic treatment.
Insights
Endostatin treatment normalized tumor vasculature and altered tumor-associated macrophage (TAM) polarization. This suggests a link between TAM shifts and vascular normalization in cancer therapy.
Area of Science:
- Oncology
- Immunology
- Vascular Biology
Background:
- Vascular normalization is a key cancer treatment concept.
- Tumor-associated macrophage (TAM) polarization influences angiogenesis and metastasis.
- The impact of anti-angiogenic agents on TAM polarization is poorly understood.
Purpose of the Study:
- To investigate TAM polarization changes during endostatin-induced tumor vascular normalization.
- To explore the relationship between endostatin, vascular normalization, and TAMs.
Main Methods:
- Murine lung cancer xenograft model treated with endostatin.
- Assessment of tumor vasculature morphology and function.
- Flow cytometry for TAMs and immunofluorescence for Tie-2-expressing monocytes (TEMs).
- Immunohistochemistry and Western blot for histidine-rich glycoprotein (HRG).
Main Results:
- Endostatin treatment led to more normal and mature tumor vessels by day six.
- Significant reduction in M2-like TAMs and TEMs, with a non-significant increase in M1-like TAMs.
- Early accumulation of HRG in tumors post-endostatin administration.
Conclusions:
- TAM polarization is linked to endostatin-induced tumor vascular normalization.
- Findings may inform novel anti-angiogenic treatment strategies.
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