Autoantibodies to endostatin in patients with breast cancer: correlation to endostatin levels and clinical outcome

Abstract

Circulating autoantibodies to self-antigens overexpressed by cancer cells are common in cancer patients. As specific proteins are expressed during neoangiogenesis, a similar phenomenon might occur with particular antigens of tumour vessels. Collagen XVIII, from which endostatin is cleaved, is highly expressed in the perivascular basement membrane of tumour-associated blood vessels and autoantibodies to endostatin have been reported in cancer patients. The present study analyses the incidence of naturally occurring autoantibodies to endostatin in the sera of breast cancer patients and their relation to endostatin serum levels and patient clinical outcome. Serum samples from 36 patients with localised breast cancer and 59 patients with a fully documented history of metastatic breast cancer were used. The immunoreactivity of serum samples was tested against purified recombinant human endostatin and endostatin levels were determined by immunoassay. We could detect anti-endostatin antibodies in the sera of 66% of the patients with localised disease and 42% of the patients with metastatic disease (P ¼ 0.03). There was no correlation between the presence of antibodies to endostatin and circulating levels of endostatin. The detection of autoantibodies to endostatin was associated with better prognosis in metastatic breast cancer patients (median survival time: 20 vs 8 months, P ¼ 0.03), as was the presence of low levels of serum endostatin (median survival time: 20 vs 9 months, P ¼ 0.007). These results show that a natural immune reaction against endostatin can occur in breast cancer patients. This could have important therapeutic implications with regard to endostatin therapy and raises the question of a possible role of this humoral reaction against endostatin in the neoplastic process.

A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

“…They are biochemically well-characterized, and many reagents and techniques are available for their detection, simplifying assay development. Until very recently, several specific autoantibodies have been detected in the sera of patients with advanced-stage breast cancer (14,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58). However, very few studies have attempted to identify and/or evaluate autoantibodies in node-negative earlystage PBC ( 2 cm) or, more importantly, in preinvasive breast cancer, for which mammography's sensitivity is decreased.…”

Inhibitory effect of endostatin combined with paclitaxel-cisplatin on breast cancer in xenograft-bearing mice

“…Bachelot et al (16) reported that patients with local breast cancer had higher serum levels of endostatin and longer median survival than those with metastasis, which suggests that endostatin may inhibit breast cancer invasion and metastasis, thereby improving the prognosis. We could treat breast cancer by blocking angiogenesis during its various stages.…”

Anti-tumor effect of recombinant plasminogen kringle 1–3 in KB cells: Histological observation and immunoprecipitation-based high performance liquid chromatography

“…This hypothesis could be supported by the fact that some peptides containing repetitive amino acid sequences such as bacterial proteins and plasminogen kringle domains can directly induce the production of antibody due to B-cell stimulation without help of T-cells in nude mouse [30,31]. Similarly, it has been reported that endostatin, an inhibitor protein of angiogenesis, can induce the production of antibody in some cancer patient, thus causing clinical failure of anti-angiogenesis therapy of endostatin [32].…”