Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2010

01-02-2010 | Brief Report

Elevated plasma endoglin (CD105) predicts decreased response and survival in a metastatic breast cancer trial of hormone therapy

Authors: M. N. Vo, M. Evans, K. Leitzel, S. M. Ali, M. Wilson, L. Demers, D. B. Evans, A. Lipton

Published in: Breast Cancer Research and Treatment | Issue 3/2010

Login to get access

Abstract

Background Endoglin (CD105) is a co-receptor for TGF-β, is expressed by human vascular endothelial cells, and plays a major role in angiogenesis. Materials and methods Pretreatment EDTA plasma from 224 metastatic breast cancer patients enrolled in a phase III 2nd-line hormone therapy trial and 50 control subjects were assayed for endoglin using an ELISA. Results The female control group (n = 50) plasma endoglin upper limit of normal was defined as the mean + 2 SD (8.7 ng/ml). The breast cancer patient plasma endoglin was 6.40 ± 2.23 ng/ml (range 3.00–19.79 ng/ml). Elevated plasma endoglin levels were detected in 26 of 224 patients (11.6%). Patients with elevated plasma endoglin had a reduced clinical benefit rate (CR + PR + Stable) (15 vs. 42%) (P = 0.01) to hormone therapy. TTP was shorter for patients with elevated plasma endoglin, but did not reach statistical significance (P = 0.2). Patients with elevated plasma endoglin had decreased overall survival (median 645 vs. 947 days) (P = 0.005). Conclusion Elevated pretreatment plasma endoglin levels predicted for decreased clinical benefit and a shorter overall survival in metastatic breast cancer patients treated with 2nd-line hormone therapy.
Literature
1.
go back to reference Barbara NP, Wrana JL, Letarte M (1999) Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-β superfamily. J Biol Chem 274(2):584–594. doi:10.1074/jbc.274.2.584 CrossRefPubMed Barbara NP, Wrana JL, Letarte M (1999) Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-β superfamily. J Biol Chem 274(2):584–594. doi:10.​1074/​jbc.​274.​2.​584 CrossRefPubMed
2.
go back to reference Cheifetz S, Bellón T, Calés C, Vera S, Bernabeu C, Massagué J, Letarte M (1992) Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem 267:19027–19030PubMed Cheifetz S, Bellón T, Calés C, Vera S, Bernabeu C, Massagué J, Letarte M (1992) Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem 267:19027–19030PubMed
3.
go back to reference Qu R, Silver MM, Letarte M (1998) Distribution of endoglin in early human development reveals high levels on endocardial cushion tissue mesenchyme during valve formation. Cell Tissue Res 292:333–343. doi:10.1007/s004410051064 CrossRefPubMed Qu R, Silver MM, Letarte M (1998) Distribution of endoglin in early human development reveals high levels on endocardial cushion tissue mesenchyme during valve formation. Cell Tissue Res 292:333–343. doi:10.​1007/​s004410051064 CrossRefPubMed
4.
go back to reference Buhring HJ, Muller CA, Letarte M, Gougos A, Saalmuller A, van Agthoven AJ, Busch FW (1991) Endoglin is expressed on a subpopulation of immature erythroid cells of normal human bone marrow. Leukemia 5:841–847PubMed Buhring HJ, Muller CA, Letarte M, Gougos A, Saalmuller A, van Agthoven AJ, Busch FW (1991) Endoglin is expressed on a subpopulation of immature erythroid cells of normal human bone marrow. Leukemia 5:841–847PubMed
5.
go back to reference Gougos A, Letarte M (1990) Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 265:8361–8364PubMed Gougos A, Letarte M (1990) Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 265:8361–8364PubMed
6.
go back to reference Gougos A, St Jacques S, Greaves A, O’Connell PJ, d’Apice AJF, Buhring HJ, Bernabeu C, van Mourik JA, Letarte M (1992) Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein of endothelial cells, leukemic cells, and syncytiotrophoblasts. Int Immunol 4:83–92. doi:10.1093/intimm/4.1.83 CrossRefPubMed Gougos A, St Jacques S, Greaves A, O’Connell PJ, d’Apice AJF, Buhring HJ, Bernabeu C, van Mourik JA, Letarte M (1992) Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein of endothelial cells, leukemic cells, and syncytiotrophoblasts. Int Immunol 4:83–92. doi:10.​1093/​intimm/​4.​1.​83 CrossRefPubMed
8.
go back to reference Li C, Guo B, Wilson PB, Stewart A, Byrne G, Bundred N, Kumar S (2000) Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int J Cancer 89(2):122–126. doi:10.1002/(SICI)1097-0215(20000320)89:2<122::AID-IJC4>3.0.CO;2-M Li C, Guo B, Wilson PB, Stewart A, Byrne G, Bundred N, Kumar S (2000) Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int J Cancer 89(2):122–126. doi:10.1002/(SICI)1097-0215(20000320)89:2<122::AID-IJC4>3.0.CO;2-M
9.
go back to reference Takahashi N, Kawanishi-Tabata R, Haba A, Tabata M, Haruta Y, Tsai H, Seon BK (2001) Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res 7(3):524–532PubMed Takahashi N, Kawanishi-Tabata R, Haba A, Tabata M, Haruta Y, Tsai H, Seon BK (2001) Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res 7(3):524–532PubMed
10.
go back to reference Li C, Gardy R, Seon BK, Duff SE, Abdalla S, Renehan A, O’Dwyer ST, Haboubi N, Kumar S (2003) Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer 88(9):1424–1431. doi:10.1038/sj.bjc.6600874 CrossRefPubMed Li C, Gardy R, Seon BK, Duff SE, Abdalla S, Renehan A, O’Dwyer ST, Haboubi N, Kumar S (2003) Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer 88(9):1424–1431. doi:10.​1038/​sj.​bjc.​6600874 CrossRefPubMed
11.
12.
go back to reference Burrows FJ, Derbyshire EJ, Tazzari PL et al (1995) Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy. Clin Cancer Res 1:1623–1634PubMed Burrows FJ, Derbyshire EJ, Tazzari PL et al (1995) Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy. Clin Cancer Res 1:1623–1634PubMed
14.
go back to reference Beresford MJ, Harris AL, Ah-See M, Daley F, Padhani AR, Makris A (2006) The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer. Br J Cancer 95:1683–1688. doi:10.1038/sj.bjc.6603491 CrossRefPubMed Beresford MJ, Harris AL, Ah-See M, Daley F, Padhani AR, Makris A (2006) The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer. Br J Cancer 95:1683–1688. doi:10.​1038/​sj.​bjc.​6603491 CrossRefPubMed
15.
go back to reference Kumar S, Ghellal A, Li C, Byrne G, Haboubi N, Wang JM, Bundred N (1999) Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res 59:856–861PubMed Kumar S, Ghellal A, Li C, Byrne G, Haboubi N, Wang JM, Bundred N (1999) Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res 59:856–861PubMed
16.
go back to reference Dales JP, Garcia S, Bonnier P, Duffaud F, Andrac-Meyer L, Ramuz O, Lavaut MN, Allasia C, Charpin C (2003) CD105 expression is a marker of high metastatic risk and poor outcome in breast carcinomas: correlations between immunohistochemical analysis and long-term follow-up in a series of 929 patients. Am J Clin Pathol 119(3):374–380. doi:10.1309/1KF54L6RB625556W CrossRefPubMed Dales JP, Garcia S, Bonnier P, Duffaud F, Andrac-Meyer L, Ramuz O, Lavaut MN, Allasia C, Charpin C (2003) CD105 expression is a marker of high metastatic risk and poor outcome in breast carcinomas: correlations between immunohistochemical analysis and long-term follow-up in a series of 929 patients. Am J Clin Pathol 119(3):374–380. doi:10.​1309/​1KF54L6RB625556W​ CrossRefPubMed
17.
go back to reference Dales JP, Garcia S, Carpentier S, Andrac L, Ramuz O, Lavaut MN, Allasia C, Bonnier P, Taranger-Charpin C (2004) Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n = 905). Br J Cancer 90:1216–1221. doi:10.1038/sj.bjc.6601452 CrossRefPubMed Dales JP, Garcia S, Carpentier S, Andrac L, Ramuz O, Lavaut MN, Allasia C, Bonnier P, Taranger-Charpin C (2004) Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n = 905). Br J Cancer 90:1216–1221. doi:10.​1038/​sj.​bjc.​6601452 CrossRefPubMed
18.
go back to reference Buzdar AU, Smith R, Vogel C et al (1996) Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer 77:2503–2513. doi:10.1002/(SICI)1097-0142(19960615)77:12<2503::AID-CNCR13>3.0.CO;2-W Buzdar AU, Smith R, Vogel C et al (1996) Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer 77:2503–2513. doi:10.1002/(SICI)1097-0142(19960615)77:12<2503::AID-CNCR13>3.0.CO;2-W
19.
go back to reference Lipton A, Ali SM, Leitzel K, Demers L, Chinchili V, Engle L, Brady C, Nalin CM, Dugan M, Carney W, Allard J (2002) Elevated serum Her-2/Neu level predicts decreased response to hormone therapy in metastatic breast cancer. J Clin Oncol 20:1467–1472. doi:10.1200/JCO.20.6.1467 CrossRefPubMed Lipton A, Ali SM, Leitzel K, Demers L, Chinchili V, Engle L, Brady C, Nalin CM, Dugan M, Carney W, Allard J (2002) Elevated serum Her-2/Neu level predicts decreased response to hormone therapy in metastatic breast cancer. J Clin Oncol 20:1467–1472. doi:10.​1200/​JCO.​20.​6.​1467 CrossRefPubMed
21.
go back to reference Li C, Guo B, Bernabeu C, Kumar S (2001) Angiogenesis in breast cancer: the role of transforming growth factor β and CD105. Microsc Res Tech 52(4):437–449. doi:10.1002/1097-0029(20010215)52:4<437::AID-JEMT1029>3.0.CO;2-G Li C, Guo B, Bernabeu C, Kumar S (2001) Angiogenesis in breast cancer: the role of transforming growth factor β and CD105. Microsc Res Tech 52(4):437–449. doi:10.1002/1097-0029(20010215)52:4<437::AID-JEMT1029>3.0.CO;2-G
22.
go back to reference Moody JL, Singbrant S, Karlsson G, Blank U, Aspling M, Flygare J, Bryder D, Karlsson S (2007) Endoglin is not critical for hematopoietic stem cell engraftment and reconstitution but regulates adult erythroid development. Stem Cells 25(11):2809–2819. doi:10.1634/stemcells.2006-0602 CrossRefPubMed Moody JL, Singbrant S, Karlsson G, Blank U, Aspling M, Flygare J, Bryder D, Karlsson S (2007) Endoglin is not critical for hematopoietic stem cell engraftment and reconstitution but regulates adult erythroid development. Stem Cells 25(11):2809–2819. doi:10.​1634/​stemcells.​2006-0602 CrossRefPubMed
23.
go back to reference Karam JA, Svatek RS, Karakiewicz PI, Gallina A, Roehrborn CG, Slawin KM, Shariat SF (2008) Use of preoperative plasma endoglin for prediction of lymph node metastasis in patients with clinically localized prostate cancer. Clin Cancer Res 14:1418–1422. doi:10.1158/1078-0432.CCR-07-0901 CrossRefPubMed Karam JA, Svatek RS, Karakiewicz PI, Gallina A, Roehrborn CG, Slawin KM, Shariat SF (2008) Use of preoperative plasma endoglin for prediction of lymph node metastasis in patients with clinically localized prostate cancer. Clin Cancer Res 14:1418–1422. doi:10.​1158/​1078-0432.​CCR-07-0901 CrossRefPubMed
24.
go back to reference Sarmiento R, Franceschini R, Meo S, Gion M, Longo R, Gasparini G (2006) Circulating vascular endothelial growth factor. In: Gasparini G, Hayes DF (eds) Biomarkers in breast cancer. Humana Press, Totowa, NJ Sarmiento R, Franceschini R, Meo S, Gion M, Longo R, Gasparini G (2006) Circulating vascular endothelial growth factor. In: Gasparini G, Hayes DF (eds) Biomarkers in breast cancer. Humana Press, Totowa, NJ
25.
go back to reference Oxmann D, Held-Feindt J, Stark AM, Hatterman K, Yoneda T, Mentlein R (2008) Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype. Oncogene 27:2567–2575. doi:10.1038/sj.onc.1211025 CrossRef Oxmann D, Held-Feindt J, Stark AM, Hatterman K, Yoneda T, Mentlein R (2008) Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype. Oncogene 27:2567–2575. doi:10.​1038/​sj.​onc.​1211025 CrossRef
Metadata
Title
Elevated plasma endoglin (CD105) predicts decreased response and survival in a metastatic breast cancer trial of hormone therapy
Authors
M. N. Vo
M. Evans
K. Leitzel
S. M. Ali
M. Wilson
L. Demers
D. B. Evans
A. Lipton
Publication date
01-02-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-008-0261-5

Other articles of this Issue 3/2010

Breast Cancer Research and Treatment 3/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine