Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels

Fonsatti, Ester; Altomonte, Maresa; Nicotra, Maria Rita; Natali, Pier Giorgio; Maio, Michele

doi:10.1038/sj.onc.1206813

Cited by 223 publications

(197 citation statements)

References 82 publications

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“…In addition, expression of CD105 is a prominent feature of newly formed blood vessels, and minimally expressed in preexisting ones. (Fonsatti et al, 2003). Expression of this marker can be also observed in non-neoplastic tissue with increased angiogenic activity such as embryonic development and wound healing (Hillen and Griffioen, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Other cells including vascular smooth muscle cells, fibroblasts, macrophages, can also express CD105 to a lesser extent (Zijlmans et al, 2009). In addition, expression of CD105 is a prominent feature of newly formed blood vessels, and minimally expressed in preexisting ones (Fonsatti et al, 2003). Expression of CD105 in blood vessels around the tumor has been shown previously (Fonsatti et al, 2003), suggesting that the role of CD105 in tumor angiogenesis.…”

Section: Introductionmentioning

confidence: 89%

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Expression of Ki67 and CD105 as Proliferation and Angiogenesis Markers in Salivary Gland Tumors

Andisheh-Tadbir¹,

Pardis²,

Ashkavandi³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: To investigate the association between CD105 and tumor cell proliferation in salivary gland tumors. Methods: In this study, 59 samples of salivary tumors from Khalili Hospital archive, including 20 cases of pleomorphic adenoma (PA), 20 cases of mucoepidermoid carcinoma (MEC) and 19 cases of adenoid cystic carcinoma, as well as 10 cases of normal salivary gland tissue, were reviewed by immunohistochemistry (IHC) for CD105 and Ki67 staining. Results: CD105 positive vessels were absent in normal salivary gland tissue in the vicinity of tumors (51.6% of all tumors were positive). There was a statistically significant difference in frequency of CD105 staining between PA and malignant tumors and between four groups of different lesions (p<0.000) being highest in MEC. Intratumoral microvessel density was also elevated in malignant neoplasms (2.61±3.1) as compared to PA (0.46±0.6). Normal salivary glands did not express Ki67. There was a statistically significant difference in frequency and percentage of Ki67 immunoreactivity in malignant neoplasms (86.5% and 10.7±10.8 respectively) compared to PA (50% and 0.78±0.2) and among the four groups values were highest in MEC (p<0.000). Conclusion: n this study, it was observed a higher rate of angiogenesis and cellular proliferation was noted in malignant tumors compared to benign tumors, but no correlation was observed between these two markers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

Expression of Ki67 and CD105 as Proliferation and Angiogenesis Markers in Salivary Gland Tumors

Andisheh-Tadbir¹,

Pardis²,

Ashkavandi³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Moreover, downstream targets of Src-signaling, such as calpain, are upregulated during TGFβ-induced EMT and are required for invadopodia formation [203,223]. Another protein, able to induce invadopodia and also involved in EMT, is endoglin, a cell surface adhesion molecule and coreceptor for TGFβ signaling [224]. Endoglin is needed for EMT during heart development, and its expression correlates with increased invasiveness of breast cancer cells via the increased formation of invadopodia [198,225].…”

Section: Invadopodia and Their Role In Emtmentioning

confidence: 99%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,548

1,314

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The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.

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“…This is negotiated through the regulation of interacting marker molecules on the cell membrane, such as vascular endothelial growth factor receptor 2 (VEGFR2) or Endoglin (1,3) and by the release of proangiogenic and antiangiogenic factors (e.g., VEGF and thrombospondin; ref. 1).…”

Section: Introductionmentioning

confidence: 99%

Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects

Palmowski

Huppert

Ladewig

et al. 2008

Molecular Cancer Therapeutics

158

113

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Molecular ultrasound is capable of elucidating the expression of angiogenic markers in vivo. However, the capability of the method for volumetric ''multitarget quantification'' and for the assessment of antiangiogenic therapy response has rather been investigated. Therefore, we generated cyanoacrylate microbubbles linked to vascular endothelial growth factor receptor 2 (VEGFR2) and A v B 3 integrin binding ligands and quantified their accumulation in squamous cell carcinoma xenografts (HaCaT-ras-A-5RT3) in mice with the quantitative volumetric ultrasound scanning technique, sensitive particle acoustic quantification. Specificity of VEGFR2 and A v B 3 integrin binding microbubbles was shown, and changes in marker expression during matrix metalloproteinase inhibitor treatment were investigated. In tumors, accumulation of targeted microbubbles was significantly higher compared with nonspecific ones and could be inhibited competitively by addition of the free ligand in excess. Also, multimarker imaging could successfully be done during the same imaging session. Molecular ultrasound further indicated a significant increase of VEGFR2 and A v B 3 integrin expression during tumor growth and a considerable decrease in both marker densities after matrix metalloproteinase inhibitor treatment. Histologic data suggested that the increasing VEGFR2 and A v B 3 integrin concentrations in tumors during growth are related to an up-regulation of its expression by the endothelial cells, whereas its decrease under therapy is more related to the decreasing relative vessel density. In conclusion, targeted ultrasound appears feasible for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive assessment of therapy effects in vivo.

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Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels

Cited by 223 publications

References 82 publications

Expression of Ki67 and CD105 as Proliferation and Angiogenesis Markers in Salivary Gland Tumors

Expression of Ki67 and CD105 as Proliferation and Angiogenesis Markers in Salivary Gland Tumors

EMT, the cytoskeleton, and cancer cell invasion

Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects

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