SVR Syngeneic Model of Angiosarcoma

Discover how Melior’s unique phenotypic screening platforms can uncover the untapped value of your candidate therapeutic

Angiosarcomas and hemangioendotheliomas are rare vascular tumors originating from endothelial cells lining blood vessels. Angiosarcomas are highly aggressive, malignant tumors, whereas hemangioendotheliomas represent a heterogeneous group of vascular neoplasms that are typically less aggressive but can range from benign to borderline or malignant behavior.

Angiosarcomas account for less than 2% of all soft tissue sarcomas but are significant due to their rapid growth, high metastatic potential, and poor prognosis. They can arise in any part of the body, but are most common in the skin, breast, liver, and deep soft tissues. Hemangioendotheliomas are even rarer and include subtypes like epithelioid hemangioendothelioma (EHE), which shows intermediate malignancy and unpredictable clinical behavior.

Medically, both tumors present significant challenges. Angiosarcomas are often diagnosed late due to nonspecific symptoms and are associated with a median survival of less than a year for advanced disease. Hemangioendotheliomas may be indolent or progressive, but effective treatments are limited, especially in metastatic cases. Current standard care for angiosarcoma includes surgical resection when possible, often combined with radiation and chemotherapy (e.g., paclitaxel or doxorubicin). Hemangioendothelioma treatment may involve surgery or targeted therapies like anti-VEGF agents, but there’s no universal consensus due to its variability.

Melior has established the SVR tumor model that represent a mouse model of angiosarcoma or hemangioendothelioma.  The SVR cell line is a derived from the MS1 cell line which is of mouse pancreatic islet endothelial origin. Interestingly although this cell line is of mouse origin it is nonetheless grown in immunocompromised mice as it is rejected by T cells in syngeneic C57BL/6 mice.  SVR is positive for endothelial markers such as CD31 and VE-cadherin, and is highly proliferative due to expression of SV40 large T antigen.  As a result, tumors form rapidly after engraftment subcutaneously or orthotopically and result in aggressive vascular tumors.  The model is suitable for studying angiogenesis and evaluation anti-angiogenic therapies as well as cytotoxic therapies towards angiosarcomas and hemangioendotheliomas.

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Chemotherapy Validation in SVR SC Model. 1 x106 SVR were injected into right flank in nude mice. The  mice were randomized into groups of untreated (n=5), paclitaxel  (20mg/kg, IP BIW; n=4), or cisplatin ( 3mg/kg, IP BIW, n=4). The treatments were begun 6 days after cell inoculation. The tumors were monitored twice per week(A). The tumor were removed and weighted at the end(B,C). Data are mean ± SEM. Paclitaxel and Cisplatin significantly inhibited SVR tumor growth; both p<0.01 by Student’s t-test.

Melior can initiate your SVR tumor model study with very short lead times and with bespoke study design to suit your needs. Including time to establish tumor-bearing mice (1-2 weeks) and typical treatment times (2-3 weeks) these studies normally run for approximately 4-5 weeks.

References:

  1. Arbiser, J. L., Bingaman, A., Durham, M., Cowan, S., Cohen, C., Zarnegar, E., … & Larsen, C. P. (2002). SVR angiosarcomas can be rejected by CD4 costimulation dependent and CD8 costimulation independent pathways. Molecular Medicine, 8, 551-558.
  2. Wagner, M. J., Lyons, Y. A., Siedel, J. H., Dood, R., Nagaraja, A. S., Haemmerle, M., … & Sood, A. K. (2021). Combined VEGFR and MAPK pathway inhibition in angiosarcoma. Scientific reports, 11(1), 9362.
  3. Funa, N. S., Reddy, K., Bhandarkar, S., Kurenova, E. V., Yang, L., Cance, W. G., … & Arbiser, J. L. (2008). Shb gene knockdown increases the susceptibility of SVR endothelial tumor cells to apoptotic stimuli in vitro and in vivo. Journal of investigative dermatology, 128(3), 710-716.

Interested in running a syngeneic angiosarcoma model study?

If you are interested in learning more about evaluating your candidate in the SVR syngeneic mouse model of angiosarcoma please contact us to start the conversation today!

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