Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line

Wang, Xin Maggie; Yu, Denise; McCaughan, Geoffrey W.; Gorrell, Mark D.

doi:10.1002/hep.20853

Cited by 164 publications

(169 citation statements)

References 47 publications

Supporting

Mentioning

156

Contrasting

Order By: Relevance

“…However, Runx2 overexpression led to reduced growth but increased invasion of IPSCs. This phenomenon has also been observed in hepatic stellate cells (HSCs) during tissue remodelling under the effects of another gene, fibroblast activation protein (FAP) (Wang et al, 2005). Fibroblast activation protein overexpression in the human HSCs leads to increased cell adhesion, migration, and invasion.…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

et al. 2007

View full text Add to dashboard Cite

Recent evidence suggests that Runt-related transcription factors play a role in different human tumours. In the present study, the localisation of the Runt-related transcription factor-2 (Runx2), its transcriptional activity, as well as its regulation of expression was analysed in human pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time PCR and immunohistochemistry were used for Runx2 expression and localisation analysis. Runt-related transcription factor-2 expression was silenced using specific siRNA oligonucleotides in pancreatic cancer cells (Panc-1) and immortalised pancreatic stellate cells (IPSCs). Overexpression of Runx2 was achieved using a full-length expression vector. TGF-b1, BMP2, and other cytokines were assessed for their potential to regulate Runx2 expression. There was a 6.1-fold increase in median Runx2 mRNA levels in PDAC tissues compared to normal pancreatic tissues (Po0.0001). Runt-related transcription factor-2 was localised in pancreatic cancer cells, tubular complexes, and PanIN lesions of PDAC tissues as well as in tumour-associated fibroblasts/stellate cells. Coculture of IPSCs and Panc-1 cells, as well as treatment with TGF-b1 and BMP2, led to increased Runx2 expression in Panc-1 cells. Runt-related transcription factor-2 overexpression was associated with decreased MMP1 release as well as decreased growth and invasion of Panc-1 cells. These effects were reversed by Runx2 silencing. In conclusion, Runx2 is overexpressed in PDAC, where it is regulated by certain cytokines such as TGF-b1 and BMP2 in an auto-and paracrine manner. In addition, Runx2 has the potential to regulate the transcription of extracellular matrix modulators such as SPARC and MMP1, thereby influencing the tumour microenvironment.

show abstract

Section: Discussionmentioning

confidence: 87%

“…Fibroblast activation protein overexpression in the human HSCs leads to increased cell adhesion, migration, and invasion. Thus, it might be speculated that Runx2 facilitates tissue remodelling via direct or indirect increase in invasion and decrease in the growth of IPSCs, as it has been suggested for FAP in HSCs (Wang et al, 2005).…”

Section: Discussionmentioning

confidence: 92%

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

et al. 2007

View full text Add to dashboard Cite

show abstract

“…DP4, DP8 and DP9 have recently been shown to act as survival factors for Ewing's sarcoma family of tumors (ESFT) through the inactivation of NPY-driven cell death within ESFT cells (16). There also appears to be non-enzymatic functions of DP4, FAP, DP8 and DP9 that are important to their roles affecting migration, proliferation and apoptosis of tumor cells (17,18).…”

Section: Introductionmentioning

confidence: 99%

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

Wilson

Abbott

2012

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Proteases, particularly serine proteases like dipeptidyl peptidase 4 (DP4) and fibroblast activation protein (FAP), play an important role in cancer invasion and angiogenesis. Aberrant expression of DP4 and FAP is associated with numerous cancers, including breast and epithelial ovarian carcinoma. We investigated the mRNA levels, protein expression and enzyme activity of the structural homologs DP8 and DP9, in addition to DP4 and FAP, in three breast carcinoma (MDA-MB-231, MDA-MB-453, MCF-7), three epithelial ovarian carcinoma (EOC) (OVCA-432, OVCA-429, SKOV3), 293T and HeLa cell lines. In addition, DP2 and prolyl endopeptidase (PEP) mRNA and enzyme levels were measured and compared in each cell line. Ubiquitous but differential expression of DP8 and DP9 mRNA and protein was observed across all cell lines. Relative to EOC, DP8 protein was lower in the breast carcinoma cell lines (p= 0.057), suggesting that DP8 may play differing roles in different cancer cell types. A strong, negative, non-reciprocal relationship was identified between DP9 protein and DP4 mRNA (r=-0.903, p=0.002) and protein (r=-0.810, p=0.015). This suggests that DP4 expression plays an important role in the post-transcriptional regulation of DP9 in breast and ovarian cancer cell lines. Overall, this study suggests a potential role for DP8 and DP9 in breast and ovarian cancer and further investigations in this area are required. IntroductionBreast and ovarian cancer are two of the most common and lethal cancers affecting women worldwide. Estimates rank breast cancer as being the number one cause of new cancer cases (1,383,000 cases, 22.9%) and cancer related deaths (458,000 deaths, 13.7%) in women worldwide in 2008. Ovarian cancer was ranked as the seventh cause of new cancer cases (225,000 cases, 3.7%) and cancer related deaths (140,000 deaths, 4.2%) in women worldwide in the same year (1). Among gynecological malignancies, epithelial ovarian carcinoma (EOC) is the most lethal to women in the world, accounting for approximately 90% of all tumors affecting the ovaries (2). Mortality from breast cancer often results from distant metastatic spread to lung, bone and lymph node tissue while diagnosis of EOC typically occurs in the late stages of disease after its spread into the peritoneal cavity or other distant sites (2), thus making it difficult for effective treatment to be administered. Although a number of risk factors for the development of breast and ovarian cancer have been identified the exact origin and pathogenesis of disease is still poorly understood (3,4). Increasing our knowledge about the fundamental biology of these diseases is needed for the development of improved diagnostic, prognostic and therapeutic interventions at all stages of disease.Enzymatic members of the DP4-like gene family, DP4, FAP, DP8 and DP9, share the rare ability to cleave N-terminal dipeptides at post-proline bonds in the penultimate position and play an important role in the biological processing of the N-termini of peptides such as chemokines, glu...

show abstract

“…32,35 For cell adhesion, 6 ϫ 10 5 Huh7 cells in 1 ml were incubated for 20 minutes on plastic coated with 10 g/ml of rat-tail collagen I (SigmaAldrich), human fibronectin (Sigma-Aldrich), or Matrigel (BD Biosciences Discovery Labware, Bedford, MA). The percentages of GFP-positive cells in adherent and nonadherent populations were obtained using flow cytometry.…”

Section: Cell Adhesion and Migration Assaysmentioning

confidence: 99%

“…The percentages of GFP-positive cells in adherent and nonadherent populations were obtained using flow cytometry. 32,35 For transwell cell migration, overnight-serum-starved Huh7 cells were placed in the upper chamber at a density of 7.5 ϫ 10 5 /ml, 1 ml per insert. The lower side of the transwell filter was coated with collagen I, fibronectin, or Matrigel.…”

Section: Cell Adhesion and Migration Assaysmentioning

confidence: 99%

Discoidin Domain Receptor 1

Song

Shackel

Wang

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell-collagen interactions in chronic liver injury.

show abstract

Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line

Cited by 164 publications

References 47 publications

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

Discoidin Domain Receptor 1

Contact Info

Product

Resources

About