Prognostic relevance of TGF‐β<sub>1</sub> and PAI‐1 in cervical cancer

Hazelbag, Suzanne; Kenter, Gemma G.; Gorter, Arko; Fleuren, Gert Jan

doi:10.1002/ijc.20512

Cited by 60 publications

(42 citation statements)

References 61 publications

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“…Multivariate analysis indicated that only plasma TGF-ß1 levels were an independent and significant prognostic factor of disease-free survival, associated with increased risk of poor prognosis. Both TGF-ß1 and Endoglin act as valuable indicators of prognosis in several tumors (56,70,(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97).…”

Section: Discussionmentioning

confidence: 99%

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Bellone

Gramigni²,

Vizio³

et al. 2010

Int J Oncol

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Abstract. The precise timing of the angiogenic switch in colorectal cancer development is still unclear. The simultaneous expression of Endoglin (CD105), transforming growth factor (TGF)-ß1 and TGF-ß receptor (R) II were quantified in surgical specimens comprising normal human colon, pre-malignant dysplastic tissue, in situ, and invasive colon cancer specimens, at mRNA and protein levels, respectively by real-time PCR and immunohistochemistry. Serum concentrations of soluble Endoglin and TGF-ß1 were evaluated. mRNA and CD105 + -microvessel density (MVD) increased significantly in dysplastic colon and carcinoma versus normal tissues; values correlated respectively with dysplasia degree and Dukes' stages. TGF-ß1 expression was significantly upregulated in most severe dysplastic adenoma specimens, while TGF-ß1 transcript and protein signals were intense in carcinoma, positively-correlated with tumor progression. TGF-ß1 RII was overexpressed in adenoma and carcinoma versus normal samples, but unrelated with dysplasia or Dukes' stage. Soluble Endoglin serum levels were equivalent in adenoma and normal tissues; in carcinoma the highest levels were in invasive tumor. Circulating TGF-ß1 levels were increased in severe dysplasia and progressed with tumor progression. Correlations between adenoma dysplasia degree and TGF-ß RII and CD105 + -MVD, and between tumor Dukes' staging and TGF-ß1 and CD105 + -MVD, were significant. TGF-ß1 and Endoglin and TGF-ß1 serum levels, TGF-ß1 staining and CD105 + -MVD were significantly and inversely associated with disease-free survival. TGF-ß1 levels were an independent and significant prognostic factor of disease-free survival. These findings suggest active angiogenesis occurs in many pre-malignant colon cases and supports more careful evaluation of different chemopreventive agents.

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Section: Discussionmentioning

confidence: 99%

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Bellone

Gramigni²,

Vizio³

et al. 2010

Int J Oncol

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“…To explore the role of TGF-b in the generation of CD105-positive vessels both the presence of CD105-positive blood vessels in the epithelial cell clusters and the number of blood vessels in the stroma were associated with the presence of PAI-1 in the epithelial cell clusters (Hazelbag et al, 2004) and the amount of fibronectin in the stroma (Hazelbag et al, 2002), both target genes of TGF-b 1 .…”

Section: Association Between Blood Vessels and Tumour-associated Macrmentioning

confidence: 99%

“…Furthermore, TGF-b 1 is known to induce VEGF expression (McMahon et al, 2006). Earlier we have reported on the expression of TGF-b 1 , plasminogen activator inhibitor (PAI)-1 and fibronectin (both target gene products of TGF-b 1 ) and avb6 (activator of TGF-b 1 ) in cervical carcinoma (Hazelbag et al, 2002(Hazelbag et al, , 2004(Hazelbag et al, , 2007.…”

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confidence: 99%

Expression of endoglin (CD105) in cervical cancer

et al. 2009

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In this study, we have investigated the role of endoglin (CD105), a regulator of transforming growth factor (TGF)-b 1 signalling on endothelial cells, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) in cervical cancer. We have measured the number and determined the location of both newly formed (CD105-positive) and the overall number of (CD31-positive) blood vessels, and bFGF and VEGF-A expression using immunohistochemistry in 30 cervical carcinoma specimens. Vascular endothelial growth factor-A mRNA expression was determined using RNA-in situ hybridisation. CD105-and CD31-positive vessels and bFGF-and VEGF-A-positive cells were predominantly present in the stroma. The presence of CD105-and CD31-positive vessels in the stroma did neither correlate with the number of VEGF-A-positive cells nor the number of bFGF-positive cells. However, the number of CD105-and CD31-positive vessels was associated with the expression of VEGF-A mRNA in the epithelial cell clusters (P ¼ 0.013 and P ¼ 0.005, respectively). The presence of CD105-positive and CD31-positive vessels was associated with the expression of avb6 (a TGF-b 1 activator; P ¼ 0.013 and P ¼ 0.006, respectively). Clinically, the number of CD105-positive vessels associated with the number of lymph node metastasis (Po0.001). Furthermore, the presence of CD105-positive vessels within the epithelial cell clusters associated with poor disease-free survival (P ¼ 0.007).

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“…35 TGF-β is another cytokine that inhibits activation, proliferation, and activity of lymphocytes. 36 This cytokine is also found in high concentration in cancer patients and is associated with tumor progression, 37 poor prognosis, 38 and lack of response to immunotherapy. 39 TGF-β can induce the production of IL-10 that leads to suppression of the immune response to cancer cells.…”

Section: Role Of Immunosuppressive Mediators and Tumor-associated Macmentioning

confidence: 99%

Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses

Kim¹,

Emi²,

Tanabe³

2005

Cancer Biology & Therapy

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Apoptotic cells can be eliminated by phagocytosis, which is mediated by antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs), through phosphatidylserine (PS) on apoptotic cells and phosphatidylserine receptor (PSR) on APCs. The phagocytosis of apoptotic cells by macrophages is strictly regulated by not only the inflammatory reaction, but also by an increase in anti-inflammatory factors such as IL-10, TGF-β, and prostaglandin E 2 (PGE 2 ), leading to an anti-inflammatory situation, whereby apoptosis contributes to a noninflammatory response. However, because PS and PSR are expressed in cancer cells, shed soluble phosphatidylserine (sPS) can interact with the PS receptor on macrophages, which promotes an anti-inflammatory response to macrophages that may lead to immune escape. The sPS derived from cancer cells also reacts with the PSR on the cancer cells to produce IL-10, TGF-β, and PGE 2 , which can cause suppression of anti-tumor immunity through the anti-inflammatory response to macrophages, which produces tumor-associated macrophages. Furthermore, sPS and TGF-β inhibit the maturation of immature DCs, resulting in a functional inhibition of DCs. The potential roles of PS and PSR in cancer cells and macrophages in immune escape mediated by sPS and anti-inflammatory factors are discussed, which may explain their dual regulation of anti-and pro-inflammatory responses during tumor progression.

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Prognostic relevance of TGF‐β₁ and PAI‐1 in cervical cancer

Abstract: Cervical carcinoma is a human papilloma virus (HPV)-

Cited by 60 publications

References 61 publications

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Expression of endoglin (CD105) in cervical cancer

Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses

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Prognostic relevance of TGF‐β1 and PAI‐1 in cervical cancer

Abstract: Cervical carcinoma is a human papilloma virus (HPV)-

Cited by 60 publications

References 61 publications

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

Expression of endoglin (CD105) in cervical cancer

Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses

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Product

Resources

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Prognostic relevance of TGF‐β₁ and PAI‐1 in cervical cancer