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Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment
Daichi Hoshina1, Riichiro Abe, Naoya Yoshioka
1Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Background:
Angiosarcoma is one of the most life-threatening neoplasms with strong resistance to conventional chemotherapy/radiotherapy; consequently, alternative therapeutic agents are urgently required. One factor in delaying the therapy development is the limitation of experimental models.
Objective:
We established a novel experimental angiosarcoma model.
Methods:
From surgically resected tissue, human AS cell line was established. Using xenograft of AS cell line, we performed therapeutic experiments with the anti-human VEGF Ab or the receptor tyrosine kinase inhibitor.
Results:
First we generated an angiosarcoma cell line, HAMON (human angiosarcoma, monoclonal), which expresses CD31 and produces tumors in immunodeficient mice. HAMON expresses VEGFR2 and that exogenous VEGF leads to HAMON proliferation in vitro. Anti-human VEGF Ab bevacizumab treatment failed to suppress HAMON proliferation in vitro and in vivo. Furthermore, the receptor tyrosine kinase inhibitor sunitinib did not suppress HAMON proliferation in vitro. Similarly, in in vivo therapeutic experiments, even high doses of sunitinib failed to inhibit tumor growth. Finally, we checked whether compensatory activation of VEGF signaling occurred after sunitinib addition. VEGF protein secretion, VEGF mRNA synthesis and VEGFR2 phosphorylation all were unaffected in HAMON after sunitinib treatment.
Conclusion:
A novel in vitro and in vivo experimental model of human angiosarcoma has been successfully established. With this model, we were able to perform therapeutic experiments. In addition, our angiosarcoma cell line, HAMON, is quite useful for identifying key molecules in angiosarcoma.
Insights
A new human angiosarcoma cell line, HAMON, was developed for research. This model showed resistance to bevacizumab and sunitinib, highlighting the need for novel therapeutic strategies against this aggressive cancer.
Area of Science:
- Oncology
- Cancer Biology
- Drug Discovery
Background:
- Angiosarcoma is a rare and aggressive cancer resistant to standard treatments.
- Limited experimental models hinder the development of new therapies for angiosarcoma.
Purpose of the Study:
- To establish a novel experimental model for human angiosarcoma.
- To evaluate the efficacy of targeted therapies in this new model.
Main Methods:
- Established a human angiosarcoma cell line (HAMON) from patient tissue.
- Utilized xenografts of the HAMON cell line in immunodeficient mice.
- Performed in vitro and in vivo therapeutic experiments using anti-VEGF antibody (bevacizumab) and a tyrosine kinase inhibitor (sunitinib).
Main Results:
- The HAMON cell line expresses CD31 and VEGFR2, and its proliferation is stimulated by VEGF.
- Bevacizumab did not inhibit HAMON proliferation in vitro or in vivo.
- Sunitinib failed to suppress HAMON proliferation in vitro and in vivo, even at high doses.
- VEGF signaling pathways remained unaffected by sunitinib treatment, suggesting no compensatory activation.
Conclusions:
- A novel in vitro and in vivo human angiosarcoma model (HAMON) has been successfully established.
- This model is valuable for therapeutic experiments and identifying key molecules in angiosarcoma.
- The resistance of HAMON to bevacizumab and sunitinib underscores the need for alternative treatment strategies.
