Dual-color imaging of angiogenesis and its inhibition in bone and soft tissue sarcoma
Katsuhiro Hayashi1, Kensuke Yamauchi, Norio Yamamoto
1Department of Surgery, University of California San Diego, San Diego, California, USA.
Background:
Angiogenesis is a critical step in tumor growth, progression, and metastasis. Soft tissue and bone sarcoma are resistant to most therapeutic approaches. Angiogenesis of these tumors may be an effective target. We hypothesized that we could inhibit tumor growth by targeting angiogenesis in a mouse model of sarcoma. We demonstrate in this report, using powerful color-coded fluorescent imageable tumor-host models, the onset of angiogenesis of these sarcomas and its inhibition.
Materials And Methods:
Transgenic mice were used as the host in which green fluorescent protein (GFP) is driven by a regulatory element of the stem cell marker nestin (ND-GFP). Nascent blood vessels express ND-GFP in this model. We visualized, by dual-color fluorescence imaging, angiogenesis of sarcoma formed by the HT-1080 human fibrosarcoma cell line expressing red fluorescent protein (RFP) in the ND-GFP mice. Tumor cells were injected into either the muscle or the bone.
Results:
Nestin was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumors, including the surrounding tissues. Immunohistochemical staining showed that CD31 colocalized in ND-GFP-expressing nascent blood vessels. The density of nascent blood vessels in the tumor was readily quantitated. The mice were given daily i.p. injections of 5 mg/kg of doxorubicin after implantation of tumor cells. Doxorubicin significantly decreased the mean nascent blood vessel density in the tumors as well as decreased tumor volume.
Conclusion:
The dual-color model of the ND-GFP nude mouse and RFP sarcoma cells is useful for the visualization and quantitation of bone and soft tissue tumor angiogenesis and evaluation of angiogenic inhibitors for such tumors. These data suggest targeting angiogenesis of sarcomas as a promising clinical approach.
Insights
Targeting tumor angiogenesis in sarcoma using a novel dual-color fluorescent model showed doxorubicin effectively reduced blood vessel density and tumor growth. This approach offers a promising strategy for treating resistant soft tissue and bone sarcomas.
Area of Science:
- Oncology
- Vascular Biology
- Biomedical Imaging
Background:
- Angiogenesis is crucial for sarcoma growth, progression, and metastasis.
- Soft tissue and bone sarcomas are often resistant to conventional therapies.
- Targeting tumor angiogenesis presents a potential therapeutic strategy.
Purpose of the Study:
- To investigate and visualize angiogenesis in a mouse model of sarcoma.
- To evaluate the efficacy of doxorubicin in inhibiting sarcoma angiogenesis and growth.
Main Methods:
- Utilized transgenic ND-GFP mice where nascent blood vessels express green fluorescent protein (GFP).
- Developed a dual-color fluorescence imaging model using RFP-expressing HT-1080 fibrosarcoma cells in ND-GFP mice.
- Quantified nascent blood vessel density and tumor volume after doxorubicin treatment.
Main Results:
- Nestin expression confirmed in proliferating endothelial cells and nascent tumor blood vessels.
- Doxorubicin treatment significantly reduced nascent blood vessel density.
- Doxorubicin administration also led to a significant decrease in tumor volume.
Conclusions:
- The dual-color fluorescence model effectively visualizes and quantifies sarcoma angiogenesis.
- Targeting angiogenesis is a promising approach for treating bone and soft tissue sarcomas.
- Doxorubicin demonstrated efficacy in inhibiting sarcoma angiogenesis and tumor growth in this model.
