Expression of endoglin (CD105) in cervical cancer

Zijlmans, Henry; Fleuren, Gert Jan; Hazelbag, Suzanne; Sier, Cornelis F.M.; Dreef, Enno J.; Kenter, G.G.; Gorter, Arko

doi:10.1038/sj.bjc.6605009

Cited by 37 publications

(28 citation statements)

References 47 publications

(58 reference statements)

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“…51 In addition, it remains to be clarified if NCAM expression can be closely associated with a down-modulation of CD105 and if this could be considered another important step to predict epithelial to mesenchymal transition. 52,53 However, our data indirectly support this hypothesis, because nNL-StCs, which are less affected by their proximity to cancer cells than HCCStCs counterpart, possessed a higher basal level of CD105 and NCAM expression.…”

Section: Tgf-b1 Induces Vascular Abnormalities In Hcccontrasting

confidence: 41%

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

Balzarini

Benetti

Invernici

et al. 2012

Laboratory Investigation

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Hepatocellular carcinoma (HCC) is a very angiogenic and malignant cancer. Conventional chemotherapy is poorly effective because of the abnormal structural organization of HCC-infiltrating vessels. In previous work, we demonstrated that HCC angiogenesis is driven by transforming growth factor beta-1(TGF-b1)/CD105 axis, stimulating liver-derived microvascular endothelial cells (Ld-MECs) migration. As TGF-b1 also affects mural cells (MCs) recruitment and maturation, we asked whether it may contribute to HCC-induced vascular abnormalities. HCC and adjacent non-neoplastic liver (nNL) biopsies obtained from 12 patients were analyzed by immunohistochemistry for angiogenic markers CD105, TGF-b1, CD44 and vascular endothelial growth factor-a (VEGFa) and for MC markers NG2, a-smooth muscle actin (aSMA) and neural cell adhesion molecule (NCAM). The same markers were also investigated by immunocytochemistry on cultured HCC-derived stromal cells (HCC-StCs) and nNL-derived StCs (nNL-StCs) isolated from the same liver biopsies. Angiogenic factors released by StCs were analyzed by ELISA and the interaction between StCs and Ld-MECs by adhesion assay. Compared with nNL, HCC biopsies showed increased angiogenic markers and aSMA that was localized in vessels. By contrast, NG2 and NCAM were substantially localized in tumor cells but absent in vessels and stroma. Cultured HCCStCs showed less expression of NG2, aSMA and NCAM. They also demonstrated a lower capacity to release angiogenic factors and adhered on Ld-MECs. HCC-StCs and nNL-StCs treated with TGF-b1 or with of HepG2 (a human hepatoma cell line) derived conditioned medium (CM), down-modulated NCAM expression, whereas anti-NCAM antibodies significantly reduced the adhesion of StCs to Ld-MECs. By further blocking TGF-b1 with anti-TGF-b1 antibodies or with Ly-364947 (a specific inhibitor TGF-b1-receptor) adhesion to Ld-MECs and NCAM expression respectively was partially restored. TGF-b1 contributes to HCC-induced vascular alterations by affecting the interaction between HCC-StCs and Ld-MECs through a down-modulation of NCAM expression. A growing tumor recruits new blood vessels to ensure a sufficient quantity of nutrients and oxygen necessary for cancer cell survival and proliferation.1 During this process, neoformed capillaries undergo abnormal maturation 2 and vascular abnormalities are often observed in tumor, mainly involving either the composition of the basement membrane or mural cells (MCs) content. 3,4 To this regard, pericytes and smooth muscle cells (SMCs) are fundamental to determine an

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Section: Tgf-b1 Induces Vascular Abnormalities In Hcccontrasting

confidence: 41%

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

Balzarini

Benetti

Invernici

et al. 2012

Laboratory Investigation

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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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“…In cervical cancer, the number of CD105-positive vessels was associated with the number of lymph node metastases. 11 MVD analyzed by endoglin expression was associated with the Gleason score, lymph node metastasis, tumor stage and preoperative prostatespecific antigen levels, in addition to being associated with survival in patients with prostate cancer. 12 Immunohistochemical expression of endoglin was also associated with poor prognosis in breast carcinoma, colon cancer, and head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Endoglin expression in upper urinary tract urothelial carcinoma is associated with intravesical recurrence after radical nephroureterectomy

et al. 2015

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Objectives: To evaluate the expression and prognostic significance of endoglin in patients with upper urinary tract urothelial carcinoma. Methods: zArchival formalin-fixed and paraffin-embedded tissues from 99 cases of primary upper urinary tract urothelial carcinomas treated with nephroureterectomy were retrieved. Tissue microarrays were constructed with triplicate tumor samples and paired non-neoplastic urothelium. Tissue microarrays were analyzed using immunohistochemistry for endoglin, and the associations between clinicopathological parameters and outcome were studied. Results: Endoglin expression was significantly higher in the endothelium of upper urinary tract urothelial carcinomas than in paired benign urothelium (P < 0.001). Endoglin expression was not associated with pathological T stage or tumor grade, and it was not associated with increased hazard ratios for cancer-specific mortality, tumor recurrence in the lymph node or distant metastasis. However, expression of endoglin was significantly associated with intravesical recurrence, when adjusting for other relevant clinicopathological variables (P = 0.015). Conclusions: Endoglin is overexpressed in the endothelium of upper urinary tract urothelial carcinomas when compared with normal urothelium, and this overexpression seems to be associated with a higher risk of intravesical recurrence. Therefore, endoglin could be a biomarker for the prediction of intravesical recurrence, as well as a potential therapeutic target.

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Expression of endoglin (CD105) in cervical cancer

Cited by 37 publications

References 47 publications

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

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

Endoglin expression in upper urinary tract urothelial carcinoma is associated with intravesical recurrence after radical nephroureterectomy

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