A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues

Wang, Ji Min; Kumar, Shant; Pye, David; Agthoven, André J. Van; Krupiński, Jerzy; Hunter, Robin D

doi:10.1002/ijc.2910540303

Cited by 156 publications

(109 citation statements)

References 19 publications

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“…These data are not in agreement with previous reports obtained with other endoglin-specific antibodies 19,20 in which several normal adult tissues were negative for this antigen. These discrepancies could be due to several reasons: the immunohistochemistry conditions used could have entailed a different sensitivity of the staining, or the antibody itself could have a different affinity for the antigen; the MAb could react with a different isoform, even though only 2 isoforms have thus far been described with a sequence difference in the intracytoplasmic tail; it could recognize an epitope that is more exposed than other epitopes on the endothelial cell surface.…”

Section: Analysis Of Endoglin Expression In Neoplastic and Normal Humcontrasting

confidence: 99%

“…4) A strong positivity was observed with this MAb, already characterized as specific for human endoglin. 20 The A11 and E9 MAbs were compared as well in immunohistochemistry on human glioblastoma and breast carcinoma samples (not shown), and the same staining pattern was observed.…”

Section: Antigen Purification and Characterizationmentioning

confidence: 75%

“…37,38 E9 MAb (mouse IgG), specific for human endoglin, was a kind gift of Dr. C. Li. 20 Normal and neoplastic human tissue samples were obtained from therapeutic surgical procedures. Each sample was divided into 2 parts: 1 was processed for conventional histopathologic diagnosis and the other was snap-frozen in liquid nitrogen and used for analyses with A11 MAb.…”

Section: Monoclonal Antibodies and Immunohistochemistrymentioning

confidence: 99%

“…19 In nonmalignant adult tissue vessels, including preneoplastic lesions, endoglin expression is weaker than in tumor vessels and often restricted to capillaries. 19,20 Endoglin is an accessory protein in the TGF-␤ receptor complex; it binds TGF-␤ 1 and 3 with high affinity and modulates cellular responses to TGF-␤ in different types of cells. [21][22][23][24][25][26] Moreover, endoglin is the mutated gene for hereditary hemorrhagic telangiectasia type 1, 27 an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent hemorrhage.…”

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confidence: 99%

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Lack of specificity of endoglin expression for tumor blood vessels

et al. 2001

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A monoclonal antibody (MAb; A11) has been raised following mouse immunization with cultured human microvascular endothelial cells. The MAb showed a strong positivity within tumor vessels in glioblastoma and breast carcinoma samples, and the distribution was consistent with antigen association with vascular endothelial cells. A purification procedure of the antigen was developed starting from DG-RSV-LT-2, an immortalized human endothelial cell line. Molecular mass, N-terminal sequence of the purified antigen and localization on endothelial cell surface allowed identification with human endoglin (CD105). Flow cytometry analysis of a group of normal and transformed cell lines showed that, besides endothelial cells and myelocytic leukemia cells already shown to be positive, fetal fibroblasts, choriocarcinoma, fibrosarcoma and rhabdomyosarcoma cell lines were also positive for this antigen. Immunohistochemic analysis of several normal adult tissues revealed a more extensive presence of the antigen in normal vessels compared to that described with previously characterized antibodies. In fact, even though the staining was weaker than in tumor tissues, all tissues were found to be positive, at least in microvessels, except for normal breast. Moreover, in some tissues (glands and reproductive tract) a positive reaction was observed in the stroma. Since endoglin has been proposed as a possible target for antiangiogenic therapy in tumor patients and our data demonstrate a sizable amount of endoglin in normal vessels and stroma, its clinical use should be carefully reevaluated.

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Section: Analysis Of Endoglin Expression In Neoplastic and Normal Humcontrasting

confidence: 99%

Section: Antigen Purification and Characterizationmentioning

confidence: 75%

Section: Monoclonal Antibodies and Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

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Lack of specificity of endoglin expression for tumor blood vessels

et al. 2001

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“…The association of CD105 with angiogenesis initially came from Wang et al (1993) who found that monoclonal antibodies to CD105 reacted strongly with the endothelium in various tumour tissues but only weakly in normal tissues. CD105 is overexpressed on endothelial cells of tissues undergoing neovascularisation and is strongly expressed in breast cancer (Bodey et al, 1998).…”

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The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer

et al. 2006

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Endoglin (CD105) is upregulated in endothelial cells of tissues undergoing neovascularisation. A greater number of CD105-positive vessels predicts poor survival in breast cancer. We examine whether CD105 expression predicts response to neoadjuvant chemotherapy. Fifty-seven women (median age 50 years, range 29 -70) received neoadjuvant chemotherapy for operable breast cancer. Immunohistochemical staining using monoclonal antibodies to CD105 and CD34 was performed on pretreatment biopsies and post-treatment surgical specimens. Individual microvessels were counted in 10 random fields at Â 200 magnification. Median counts were correlated with clinical and pathological response using the Mann -Whitney U-test. Forty-five out of fifty-seven patients (79%) responded clinically, 22 (39%) responded pathologically. On pretreatment biopsies, clinical responders had significantly lower median CD105-positive vessel counts than nonresponders (median counts 5 and 9.3/high-power field (hpf), median difference ¼ 4.0/ hpf, 95% CI 0.5 -8.0/hpf, P ¼ 0.02). For pathological responders and nonresponders, median counts were 4.8 and 5.5/hpf (median difference -0.5/hpf, 95% CI ¼ À2.5 -2.0/hpf, P ¼ 0.77). CD34 expression (total microvessel density) did not correlate with response. Pretreatment CD105 expression predicts for clinical response to chemotherapy, with a lower initial count being favourable. Patients with high baseline new vessel counts or increased counts after conventional therapy may benefit from additional antiangiogenic therapy. British Journal of Cancer (2006) The formation of new blood vessels, angiogenesis, is a requirement for the growth of tumours and for the development of metastases (Folkman, 1990). Angiogenic activity is heterogeneous within a tumour type, and surrogate markers such as microvessel density are commonly used to quantify angiogenesis. Microvessel density can be scored by immunohistochemistry using antibodies against factor VIII-associated antigen, PECAM-1/CD 31 or CD 34. This technique was developed by Weidner et al (1991), initially using antibodies against factor VIII-related antigen that stain mainly mature vessels. The more recent use of antibodies against CD31 (platelet endothelial cell adhesion molecule) and CD34 also stain immature vessels and are thus referred to as panendothelial markers. The assessment of microvessel density has been related to the presence of metastases (Weidner et al, 1991) and overall survival in breast cancer (Bosari et al, 1992). A meta-analysis of 43 independent studies by Uzzan et al (2004) revealed that a high microvessel density significantly predicts for a poor survival (relative risk ¼ 1.54, 95% CI ¼ 1.29 -1.84).Endoglin (CD105) is a cell-surface glycoprotein that binds with high affinity to transforming growth factors (TGF) b1 and b3 (Cheifetz et al, 1992) which are involved in regulation of cell differentiation and proliferation in most cell types. The association of CD105 with angiogenesis initially came from Wang et al (1993) who found that monoclonal antibo...

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