Endostatin Concentrations in Healthy Dogs and Dogs with Selected Neoplasms

Abstract

Endostatin prevents angiogenesis and tumor growth by inhibiting endothelial cell proliferation and migration. The purpose of this study was to determine serum endostatin concentrations in 53 healthy dogs and in 38 dogs with confirmed malignant neoplasms. Endostatin concentration was determined with a competitive enzymatic immunoassay (EIA) with rabbit polyclonal antibody generated against a recombinant canine endostatin protein. Both the presence of cancer and increasing age were associated with increased serum concentration of endostatin. Endostatin concentration in healthy dogs was 87.7 Ϯ 3.5 ng/mL. Upper and lower limits of the reference range for serum endostatin concentration in healthy dogs were 60 and 113 ng/mL. Dogs with lymphoma (LSA) and hemangiosarcoma (HSA) had endostatin concentrations of 107 Ϯ 9.3 ng/mL. In conclusion, this study demonstrates that endostatin can be quantified in dogs and that endostatin concentrations are high in dogs with HSA and LSA.Key words: Angiogenesis; Neoplasia; Vascular biology.A ngiogenesis plays an integral role in a variety of normal physiologic states and has been recognized for its role in the pathogenesis of diseases such as atherosclerosis and neoplasia. 1,2 Biologic tumor behavior is linked to the ability of neoplasms to induce endothelial cell growth and organization, with tumor growth being dependent on regulation of angiogenesis. [3][4][5][6] With in vivo and in vitro models, researchers have shown that without recruitment of a new blood supply, tumor size is limited to a few cubic millimeters because of a lack of energy substrate delivery, and expression of the metastatic phenotype is delayed or absent. 3,5 Alternatively, aggressive malignancies with high distant metastatic potential suppress anti-angiogenic factors, stimulate local production of angiogenic substances by normal host tissues, and endogenously produce active angiogenic compounds. 2,4,7 Endostatin, a carboxy-terminal fragment of collagen XVIII originally isolated from a murine hemangioendothelioma cell line, inhibits angiogenesis by preventing endothelial proliferation and migration. 3,5 Anti-neoplastic properties of endostatin have been demonstrated in vitro and in several animal models with multiple neoplastic cell lineages, and increased circulating endostatin concentrations may be associated with the development or recurrence of neoplasia in mice and humans. 3,5,[8][9][10] Hemangiosarcoma (HSA) is an aggressive malignancy primarily affecting older male, large-breed dogs. 11-17 HSA typically affects the spleen, right atrium, and skin or sub-