The role of transforming growth factor-β (TGF-β) in epithelial ovarian cancer progression via immunosuppression

2019 ◽  
Vol 154 ◽  
pp. 56
Author(s):  
B.M. Roane ◽  
S. Meza-Perez ◽  
I. Betella ◽  
W. Goldsberry ◽  
R.C. Arend
2004 ◽  
Vol 14 (1) ◽  
pp. 82-88
Author(s):  
M. SÖNMEZER ◽  
M. GÜNGÖR ◽  
A. Ensari ◽  
F. Ortaç

We aimed to evaluate the prognostic significance of microvessel density (MVD), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGFβ), as well as to find out the relationship between MVD, and VEGF and TGFβ in epithelial ovarian cancer (EOC). Surgical specimens of 47 patients with stage I–IV primary EOC, who underwent extended surgical staging according to FIGO, were investigated. Five-μm thick tissue sections were immunostained with antibody to factor VIII-related antigen, and MVD was assessed at three separate areas of ×200 magnification. Expressions for VEGF and TGFβ were evaluated by immunohistochemical staining using related monoclonal antibodies. Results were correlated with clinicopathologic factors and survival. We did not find any correlation between MVD and clinicopathologic factors, or patient survival. Similarly, there was no association between the degree of VEGF staining and survival or clinicopathologic factors, except preoperative ascites volume, which was higher in patients showing moderate and intense VEGF staining than those with weak VEGF staining (P = 0.052). The expression of TGFβ was inversely correlated with preoperative CA-125 levels (P < 0.05). Furthermore, there was no correlation between MVD and the staining intensity of VEGF or TGFβ. In conclusion, angiogenesis does not appear as a prognostic factor in EOC. We suggest that VEGF is an important mediator of ascites formation, and that TGFβ, which is supposed to have tissue-specific actions in tumorigenesis, may have growth-inhibitory functions in EOC.


1999 ◽  
Vol 15 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Ali Khalifa ◽  
Samar K. Kassim ◽  
Maha I. Ahmed ◽  
Salah T. Fayed

The role of transforming growth factor-β(TGF-β) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-βby enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-β, nitrate, and SPF were significant among different groups (X2= 12.01, P = 0.0025, X2= 67.42, P = 0.000, X2= 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2= 17.6, P = 0.000). A significant correlation was shown between TGF-â, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-β(290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-βhad 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-βabove the cut-off had worse prognosis (X2= 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-βand NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-βcould be of prognostic significance.


2001 ◽  
Vol 80 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Gustavo C. Rodriguez ◽  
Camille Haisley ◽  
Jean Hurteau ◽  
Tammy L. Moser ◽  
Regina Whitaker ◽  
...  

Author(s):  
Min Zhao ◽  
Zhiying Su ◽  
Shiyang Zhang ◽  
Liangjin Zhuang ◽  
Yudi Xie ◽  
...  

Ovarian cancer (OC) is one of the most common gynecological malignancies. MicroRNAs (miRs) play a crucial role in the development and progression of OC, but the underlying mechanism remains largely unclear. Our study investigated the regulatory role of miR-148a in OC cell proliferation and invasion. We found that miR-148a was significantly downregulated in OC tissues compared to their matched adjacent nontumor tissues. In addition, its expression was also reduced in OC cell lines (SKOV3, ES-2, OVCAR, and A2780) compared to normal ovarian epithelial cells. Overexpression of miR-148a caused a significant decrease in OC cell proliferation and invasion, as well as reduced MMP9 protein levels. Transforming growth factor-β-induced 2 (TGFI2) was further identified as a target gene of miR-148a, and its protein expression was downregulated in OC cells after miR-148a overexpression. Restoration of TGFI2 attenuated the suppressive effects of miR-148a on OC cell proliferation and invasion. Moreover, we found that TGFI2 was remarkably upregulated in OC tissues when compared with their matched adjacent nontumor tissues, and observed a reverse correlation between miR-148a and TGFI2 expression in OC tissues. On the basis of these findings, we suggest that miR-148a inhibits OC cell proliferation and invasion partly through inhibition of TGFI2. Therefore, our study highlights the importance of the miR-148a/TGFI2 axis in the malignant progression of OC.


2006 ◽  
Vol 2 (6) ◽  
pp. 743-763 ◽  
Author(s):  
Amy J Galliher ◽  
Jason R Neil ◽  
William P Schiemann

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