Introduction

Canine splenic hemangiosarcoma (cHSA) is a highly malignant solid tumor that results in near universal fatality. Historically, cytotoxic therapies have been used to minimize residual disease following surgery and yet survival times in these dogs remain disappointing. An alternative strategy that has received limited attention is the exploration of metabolic vulnerabilities that might exert cytostatic effects; reducing cHSA proliferation and progression. The phenomenon of glutamine addiction has been documented in several human cancers, whereby glutamine is a valuable anaplerotic resource utilized in several metabolic pathways. Tumor dependency on glutamine becomes so great that its removal induces cellular senescence and death. Metabotropic glutamate receptor 1 (mGluR1) is a G-coupled protein receptor overexpressed in several cancer types and participates in an autocrine/paracrine feedback loop that promotes cancer cell proliferation. In this study, we seek to understand the influence of glutamine metabolism and mGluR1 inhibition on canine hemangiosarcoma.

Methods

Six cHSA immortalized cell lines and 36 cHSA tumor and metastatic mass biopsies were assessed for mGluR1 expression. Cell line sensitivity to two mGluR1 small molecule inhibitors was evaluated by cellular proliferation assays.

Results

All cHSA cells and biopsy samples express mGluR1. Proliferation in all treated cell lines is reduced when subjected to one of two mGluR1 inhibitor molecules, with an average IC50 of 62.43 (mu)M and 56.49 (mu)M.

Conclusion

Expression of mGluR1 is detected in cHSA immortalized cell lines and biopsy samples. All tested cHSA cell lines tested experience reduced proliferation when treated with mGluR1 inhibitor molecules.

Funding Information

Funded by VCS Resident Research Grant.