Expression and significance of transforming growth factor-β1 in epithelial ovarian cancer and its extracellular matrix

Abstract

The aim of the present study was to investigate the expression and significance of transforming growth factor-β1 (TGF-β1) in the cytoplasm and extracellular matrix (ECM) of epithelial ovarian cancer cells. The expression of TGF-β1 protein was detected in paraffin-embedded sections of 25 normal ovarian epithelial tissues, 10 benign epithelial cysts and 72 epithelial ovarian cancer specimens, using the Strept Avidin Biotin Peroxidase Complex immunohistochemistry method. In addition, the expression of TGF-β1 mRNA in normal fibroblasts (NFs) and ovarian cancer-associated fibroblasts (CAFs) was assessed using semi-quantitative polymerase chain reaction (PCR). TGF-β1 protein was expressed in the cytoplasm and ECM, and no significant difference was identified between normal and benign ovarian tissues (P>0.05). However, the cytosolic expression of TGF-β1 declined gradually between the benign ovarian tumor and epithelial ovarian cancer, while its expression in the ECM significantly increased (P<0.05). The expression of TGF-β1 in the cytoplasm and ECM in epithelial ovarian cancer was found to negatively correlate with tumor differentiation, however, it was positively associated with the clinical stages. The positive rates of TGF-β1 in the cytoplasm and ECM between ovarian cancers in clinical stages I-II and III-IV were significantly different (P<0.05). Furthermore, the PCR data indicated that the relative expression of TGF-β1 mRNA in ovarian CAFs (1.0270±0.0539) was significantly higher than that in NFs (0.7131±0.0186). Therefore, the expression of TGF-β1 was identified to be associated with the development and progression of epithelial ovarian cancer, and the high expression of TGF-β1 in the ECM may be associated with the invasion and metastasis of ovarian cancer.

Keywords: extracellular matrix; ovarian cancer; transforming growth factor-β1.

Figure 1

Expression of transforming growth factor-β1 was (+++) in the cytoplasm and (+) in the extracellular matrix of normal ovarian epithelial cells (magnification, ×200). Sections with <5% positive cells scored 0; 5–25% positive cells scored 1; 26–50% positive cells scored 2; 51–75% positive cells scored 3; and >75% positive cells scored 4. To dermine the positivity of a sample 0–2 corresponds to (−), 3–4 to (+), 5–8 to (++) and 9–12 to (+++).

Figure 2

Expression of transforming growth factor-β1 was (++) in the cytoplasm and (−) in the extracellular matrix of benign ovarian epithelial cells (magnification, ×200). Sections with <5% positive cells scored 0; 5–25% positive cells scored 1; 26–50% positive cells scored 2; 51–75% positive cells scored 3; and >75% positive cells scored 4. To dermine the positivity of a sample 0–2 corresponds to (−), 3–4 to (+), 5–8 to (++) and 9–12 to (+++).

Figure 3

Expression of transforming growth factor-β1 was (++) in the cytoplasm and (+) in the extracellular matrix of epithelial ovarian cancer cells (magnification, ×200). Sections with <5% positive cells scored 0; 5–25% positive cells scored 1; 26–50% positive cells scored 2; 51–75% positive cells scored 3; and >75% positive cells scored 4. To dermine the positivity of a sample 0–2 corresponds to (−), 3–4 to (+), 5–8 to (++) and 9–12 to (+++).

Figure 4

Expression of transforming growth factor-β1 was (−) in the cytoplasm and (−) in the extracellular matrix of epithelial ovarian cancer cells (magnification, ×200). Sections with <5% positive cells scored 0; 5–25% positive cells scored 1; 26–50% positive cells scored 2; 51–75% positive cells scored 3; and >75% positive cells scored 4. To dermine the positivity of a sample 0–2 corresponds to (−), 3–4 to (+), 5–8 to (++) and 9–12 to (+++).

Figure 5

Electrophoresis detection of the polymerase chain reaction products of TGF-β1 mRNA in ovarian CAFs and NFs. β-actin served as an internal reference. CAF, cancer-associated fibroblast; NF, normal fibroblast; TGF-β1, transforming growth factor.