Transforming growth factor-1 promotes the transcriptional activation             of plasminogen activator inhibitor type 1 in carcinoma-associated fibroblasts.
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.
Orthopedic Department, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, PR China.
Yu
Y
Zhu
Wan-Le
WL
Yin
Yu-Feng
YF
Ba
Lin
L
Tian
Zhi-Qiang
ZQ
Gu
Ming-Sheng
MS
Zhang
Chu-Nan
CN
Zhong
D000199:Actins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
C541116:ACTA2 protein, human; D000199:Actins; D017395:Plasminogen Activator Inhibitor 1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor