Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours

Fonsatti, Ester; Nicolay, Hugues J. M.; Altomonte, Maresa; Covre, Alessia; Maio, Michele

doi:10.1093/cvr/cvp332

Cited by 147 publications

(167 citation statements)

References 96 publications

(147 reference statements)

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“…As the TGF-β accessory receptor III, CD105 promotes neovascularization by binding with TGF-β1 and TGF-β3 with high affinity as reported by Fonsatti et al (36) and Warrington et al (37).…”

Section: Discussionmentioning

confidence: 65%

Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization

et al. 2015

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Abstract. The ability of tumor cells to autonomously generate tumor vessels has received considerable attention in recent years. However, the degree of autonomy is relative. Meanwhile, the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on tumor neovascularization has not been fully elucidated. The present study aimed to illuminate whether cell fusion between glioma stem cells and BMSC is involved in glioma neovascularization. BMSCs were isolated from transgenic nude mice, of which all nucleated cells express green fluorescent protein (GFP). The immunophenotype and multilineage differentiation potential of BMSC were confirmed. SU3 glioma stem/progenitor cells were transfected with red fluorescent protein (SU3-RFP cells). In a co-culture system of BMSC-GFP and SU3-RFP, RFP + /GFP + cells were detected and isolated by dual colors using FACS. The angiogenic effect of RFP + /GFP + cells was determined in vivo and in vitro. Flow cytometry analysis showed that BMSC expressed high levels of CD105, C44, and very low levels of CD45 and CD11b. When co-cultured with SU3-RFP, 73.8% of cells co-expressing RFP and GFP were identified as fused cells in the 5th generation. The fused cells exhibited tube formation ability in vitro and could give rise to a solid tumor and form tumor blood vessels in vivo. In the dual-color orthotopic model of transplantable xenograft glioma, yellow vessel-like structures that expressed CD105, RFP and GFP were identified as de novo-formed vessels derived from the fused cells. The yellow vessels observed in the tumor-bearing mice directly arose from the fusion of BMSCs and SU3-RFP cells. Thus, cell fusion is one of the driving factors for tumor neovascularization.

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Section: Discussionmentioning

confidence: 65%

Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization

et al. 2015

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“…Such a correlation for endothelial cells but not for tumor cells has also been identified in oral squamous cell carcinoma, 8,34 where in vitro studies further demonstrated that BCL2 8 In xenografted squamous cell carcinoma cell lines, BCL2 crosstalk between endothelial and tumor cells through VEGFA leads to tumor growth and metastatic development. 8,9,11,35 A neoangiogenic subtype of endothelial cells, expressing CD105, a TGFb-receptor type III auxiliary receptor, 13 has been identified. [36][37][38] CD105 expression on endothelial cells is related to tumor progression in squamous cell carcinoma, 16 glioblastomas, 15 and meningiomas.…”

Section: Discussionmentioning

confidence: 99%

“…12 Neoangiogenic endothelial cells can be characterized in solid tumor by expression of CD105, a TGFbR type III auxiliary receptor. 13 In meningiomas, glioblastomas, and squamous cell carcinoma, CD105 expression on endothelial cells is related to neoangiogenesis and to tumor progression. [14][15][16] CD105 is also expressed by endothelial cells in the primary central nervous system lymphomas and correlates with survival.…”

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confidence: 99%

BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma

et al. 2012

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The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in wellcharacterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34 þ CD105 þ endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34 þ endothelial cells, but not in CD3 þ CD10 þ lymphoma cells, or in CD34 þ endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34 þ CD105 þ neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105 þ neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma.

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“…Ya-Kai Huang 1 *, Hong Liu 2 , Xin-Zheng Wang 3 , Shan Zhu 3 angiogenesis (Fonsatti et al, 2010;Fujiwara et al, 2013). Immunostaining of CD105 is used to label MVD.…”

Section: Annexin A2 and Cd105 Expression In Pancreatic Ductal Adenocamentioning

confidence: 99%

Annexin A2 and CD105 Expression in Pancreatic Ductal Adenocarcinoma is Associated with Tumor Recurrence and Prognosis

Huang

Hong²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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To investigate the value of expression of annexin A2, microvessel density (MVD) and CD105 in pancreatic ductal adenocarcinoma (PDAC) tissues and adjacent normal tissues, immunohistochemical staining was used. The positive expression rate of Annexin A2 and the MVD in pancreatic ductal adenocarcinoma tissues was higher than that in in adjacent normal tissues (p<0.005). Expression of Annexin A2 and MVD correlated with histological grade (p<0.05). MVD of cancers in TNM stage Ⅱb was higher than that in TNM stageⅠ~Ⅱa (p<0.026). Cancerous tissues with Annexin A2 staining grade 3+ had lower MVD than the tissues with the other Annexin A2 staining grade (p<0.05). Patients with high MVD had worse prognosis. However , our study did not confirm Annexin A2 was an independent risk factor for patients with PDAC. We confirmed MVD labeled by CD105 was an independent risk factor for patients with PDAC and had moderate predictive value of prognosis.

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Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours

Cited by 147 publications

References 96 publications

Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization

Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization

BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma

Annexin A2 and CD105 Expression in Pancreatic Ductal Adenocarcinoma is Associated with Tumor Recurrence and Prognosis

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