title: Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin.
abstract: In this report, we present data indicating that the increased serum endoglin (EDG; CD105) quantitated by a double-antibody sandwich assay is associated with metastasis in patients with solid tumors including colorectal and breast carcinomas. In addition, we show that chemotherapy exerts a suppressive effect on the serum EDG. EDG is a proliferation-associated cell membrane antigen of human vascular endothelial cells. Furthermore, EDG is essential for angiogenesis. We generated two anti-EDG monoclonal antibodies (mAbs), termed SN6a and SN6h, defining different epitopes of EDG and developed a double-antibody sandwich assay to quantitate serum EDG in patients with solid tumors. SN6h possesses an exceedingly high antigen-binding avidity (K, 1.38 x 10(11) liters/mol), whereas SN6a possesses an ordinary avidity for a mAb directed to a cell surface antigen (K, 2.85 x 10(8) liters/mol). We measured serum samples from 101 patients with solid tumors (34 colorectal cancers, 16 breast cancers, and 51 other cancers), 8 patients with benign diseases, and 31 healthy volunteers. The serum level of EDG was significantly elevated in the patients with metastatic cancers. The mean serum EDG in the 42 metastasis-negative patients was 34.0 +/- 26.8 ng/ml (median value, 27.9 ng/ml), whereas the value in the 59 metastasis-positive patients was 63.8 +/- 72.5 ng/ml (median value, 37.2 ng/ml). The difference in EDG levels between the two groups was statistically significant (P = 0.012). Of the colorectal cancer patients, the difference in EDG levels between the 19 metastasis-negative patients and the 15 metastasis-positive patients was statistically significant (P = 0.02). In addition, the difference between the normal control (n = 31) and the 15 metastasis-positive colorectal cancer patients was statistically significant (P = 0.04). Of the breast cancer patients, the difference in EDG levels between the 11 metastasis-positive patients and the normal control was statistically significant (P < 0.005). In additional studies, we found that chemotherapy suppressed serum EDG levels in cancer patients. Of the 54 metastasis-positive patients with solid tumors, the mean serum EDG in the 32 chemotherapy-receiving [chemotherapy(+)] patients was 44.7 +/- 41.9 ng/ml (median value, 36.1 ng/ml), whereas the value in the 22 chemotherapy(-) patients was 102.4 +/- 99.5 ng/ml (median value, 64.8 ng/ml). The difference in serum EDG between the two groups is statistically significant (P < 0.005). In the majority of metastasis-positive patients who were not receiving chemotherapy, serum EDG was elevated. The results suggest that serum EDG may be a useful marker for monitoring early signs of metastasis and cancer relapse in a long-term follow-up of solid tumor patients.
authors: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors: N
authors: N
authors: Takahashi
authors: R
authors: R
authors: Kawanishi-Tabata
authors: A
authors: A
authors: Haba
authors: M
authors: M
authors: Tabata
authors: Y
authors: Y
authors: Haruta
authors: H
authors: H
authors: Tsai
authors: B K
authors: BK
authors: Seon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000915:Antibody Affinity; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001667:Binding, Competitive; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology*; D004306:Dose-Response Relationship, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D000071063:Endoglin; D000939:Epitopes / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011233:Precipitin Tests; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface; D012008:Recurrence; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D000939:Epitopes; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1