Transforming growth factor-1 promotes the transcriptional activation of plasminogen activator inhibitor type 1 in carcinoma-associated fibroblasts

Zhu,Yu; Yin,Wan-Le; Ba,Yu-Feng; Tian,Lin; Gu,Zhi-Qiang; Zhang,Ming-Sheng; Zhong,Chu-Nan

doi:10.3892/mmr.2012.1020

Transforming growth factor-1 promotes the transcriptional activation of plasminogen activator inhibitor type 1 in carcinoma-associated fibroblasts

Authors:
- Yu Zhu
- Wan-Le Yin
- Yu-Feng Ba
- Lin Tian
- Zhi-Qiang Gu
- Ming-Sheng Zhang
- Chu-Nan Zhong
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Affiliations: Orthopedic Department, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China , Orthopaedic Trauma and Microsurgery Department, Zhengzhou People's Hospital, Zhengzhou, Henan 450014, P.R. China , Department of Thoracic Surgery, Affiliated Cancer Hospital of Zhengzhou University (Cancer Hospital of Henan Province), Zhengzhou, Henan 450014, P.R. China , Department of Internal Medicine, Zhengzhou Ninth People's Hospital, Zhengzhou, Henan 450014, P.R. China , Department of Nuclear Magnetic Resonance Imaging, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China, Orthopedic Department, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China
Published online on: August 7, 2012 https://doi.org/10.3892/mmr.2012.1020
Pages: 1001-1005

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Abstract

Carcinoma-associated fibroblasts (CAFs) play a pivotal role in promoting the growth, invasion and metastasis of tumor cells. However, to date little is known about the oncogenic mechanisms of CAFs. This study aimed to identify the microenvironmental factors involved in tumor development and progression directed by CAFs in liver metastases. Tissue samples collected from 20 patients with colorectal liver metastases were used in this study. Histological and morphological characterization of the samples was performed using hybridization and immunohistological assays. The mRNA expression of α-smooth muscle actin (α-SMA) was measured by northern blotting. The expression of plasminogen activator inhibitor type 1 (PAI-1) was measured by enzyme-linked immunosorbent assay (ELISA). As a result, co-expression of Thy-1 (CD90) and α-SMA was identified in CAFs, while normal liver samples were negative for α-SMA and Thy-1. Compared with epidermal growth factor (EGF) and tumor necrosis factor (TNF) incubation, the expression of α-SMA increased significantly following transforming growth factor-1 (TGF-1) incubation (P<0.05), while platelet-derived growth factor (PDGF) caused a significant suppression of α-SMA expression (P<0.05). PAI-1 expression was significantly lower in unstimulated fibroblasts compared to TGF-1-treated fibroblasts (P<0.01). The levels of PAI-1 transcription were significantly higher in CAFs from the patient samples compared with the healthy controls. Taken together, our findings suggest that CAFs may be important in migration, matrix degradation, invasion and angiogenesis of tumors, and TGF-1 may promote the activation of PAI-1 transcription in CAFs.

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