Imaging of tumour neovasculature by targeting the TGF-β binding receptor endoglin

Bredow, Sebastian; Lewin, M.; Hofmann, B.; Marecos, Edgardo; Weissleder, Ralph

doi:10.1016/s0959-8049(99)00335-4

Cited by 107 publications

(51 citation statements)

References 26 publications

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“…15 Two recent studies have shown tumor imaging and biodistribution in animal models using radiolabeled antiendoglin antibodies. Fonsatti et al 32 described the uptake in dog mammary adenocarcinoma using an antihuman endoglin MAb; Bredow et al 31 used a rat antimouse endoglin MAb to target B16 melanoma in mouse; and in this study the uptake in several tissues (heart, kidney, liver) was higher than in the tumor. This species with respect to humans shows an apparently higher expression of the antigen in normal organs.…”

Section: Analysis Of Endoglin Expression In Neoplastic and Normal Hummentioning

confidence: 62%

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 Hummentioning

confidence: 62%

Lack of specificity of endoglin expression for tumor blood vessels

et al. 2001

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“…A diagnosis of ductal adenocarcinoma was verified by surgical excision 10 days later, and the dogs showed no systemic side effects during the 3-month follow-up period. Others used indium-111 -labeled anti-endoglin mAbs to identify B16 melanomabearing tumors in mice by in vivo scintigraphy (58). Another group of investigators conjugated microbubbles, which can be visualized by ultrasonography, to anti-endoglin mAbs (59).…”

Section: Endoglin In Diagnosis and Therapymentioning

confidence: 99%

Endoglin (CD105): A Marker of Tumor Vasculature and Potential Target for Therapy

Dallas

Samuel

Xia

et al. 2008

Clinical Cancer Research

306

296

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Endoglin (CD105) is an accessory protein of the transforming growth factor-h receptor system expressed on vascular endothelial cells. Mutation of the endoglin gene is associated with hereditary hemorrhagic telangiectasias, or Osler-Weber-Rendu syndrome, and has been studied extensively in the context of this disease.The expression of endoglin is elevated on the endothelial cells of healing wounds, developing embryos, inflammatory tissues, and solid tumors. Endoglin is a marker of activated endothelium, and its vascular expression is limited to proliferating cells. Recent studies identified endoglin expression in several solid tumor types, with the level of expression correlating with various clinicopathologic factors including decreased survival and presence of metastases. Attempts to target endoglin and the cells that express this protein in tumor-bearing mice have yielded promising results.

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“…There are also differences in reactivity to endothelial cells depending on tumor localization [22][23][24] . However, in colorectal cancer, other studies showed that, with cancer progression, endoglin signaling was lost in most of the epithelial cancer cells which became refractory to the TGF-β growth inhibiting properties [25][26][27][28][29] . All these factors could lead to differences in diagnostic, prognostic and therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Tumor neoangiogenesis detection by confocal laser endomicroscopy and anti-CD105 antibody: Pilot study

Ciocalteu¹,

Săftoiu²,

Pirici³

et al. 2015

WJGO

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AIM:To evaluate neoangiogenesis in patients with colon cancer by two fluorescently labeled antibodies on fresh biopsy samples imaged with confocal laser endomicroscopy (CLE). . When using the anti-CD31 antibody, the average diameter of vessels in the normal colon tissue was 7.67 ± 0.5 μm and the vessel density was 3191.60 ± 387.8 vessels/mm 3 , while in the tumors we obtained an average diameter of 10.88 ± 0.8 μm and a vessel density of 4707.30 ± 448.85 vessels/mm 3 . Thus, there were more vessels stained with CD31 than CD105 (P < 0.05). The average vessel diameter was similar for both CD31 and CD105 staining. A qualitative comparison between CLE vs immunohistochemistry lead to similar results. CONCLUSION:Specific imaging and quantification of tumor microvessels are feasible in human rectal cancer using CLE examination and CD105 immunostaining of fresh tissue samples. Core tip: We evaluated CD105 expression from fresh tissue samples of human rectal adenocarcinoma, using confocal laser endomicroscopy (CLE). While vessels marked with fluorescent CD31 were visible in both normal and malignant tissue, CD105 was predominantly expressed in tumor lesions, having reduced affinity for normal rectal mucosa. Our data showed that CLE using CD105 antibody for tumor vascular network imaging is feasible and that CD105 represents a more specific marker for rectal cancer neoangiogenesis than panendothelial markers. To our knowledge, this is the first study to report the use of fluorescently-labeled CD105 antibody in conjunction with CLE in patients with rectal tumor.

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Imaging of tumour neovasculature by targeting the TGF-β binding receptor endoglin

Cited by 107 publications

References 26 publications

Lack of specificity of endoglin expression for tumor blood vessels

Lack of specificity of endoglin expression for tumor blood vessels

Endoglin (CD105): A Marker of Tumor Vasculature and Potential Target for Therapy

Tumor neoangiogenesis detection by confocal laser endomicroscopy and anti-CD105 antibody: Pilot study

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