Transcriptional Regulation of Seprase in Invasive Melanoma Cells by Transforming Growth Factor-β Signaling

Tulley, Shaun; Chen, Wen Tien

doi:10.1074/jbc.m114.568501

Cited by 29 publications

(36 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HERS cells undergo EMT in the presence of TGF-β1 (Akimoto et al, 2011) which is associated with HERS fragmentation and reduction in E-cadherin expression. Since FAPα expression is regulated by TGF-β1 (Tulley and Chen, 2014), we suggest that FAPα positive epithelial cells in HERS remnants could be part of a TGF-β1 driven EMT process. Collagenase type I activity exerted by FAPα could promote disintegration of the epithelial sheath enabling cell migration.…”

Section: Discussionmentioning

confidence: 88%

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Driesen

Hilkens

Smisdom

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Fibroblast activation protein-α (FAPα) is a membrane protein with dipeptidyl-peptidase and type I collagenase activity and is expressed during fetal growth. At the age of adolescence, FAPα expression is greatly reduced, only emerging in pathologies associated with extracellular matrix remodeling. We determined whether FAPα is expressed in human dental tissue involved in root maturation i.e., dental follicle and apical papilla and in dental pulp tissue. The dental follicle revealed a high concentration of FAPα and vimentin-positive cells within the stromal tissue. A similar observation was made in cell culture and FACS analysis confirmed these as dental follicle stem cells. Within the remnants of the Hertwigs' epithelial root sheath, we observed FAPα staining in the E-cadherin positive and vimentin-negative epithelial islands. FAPα-and vimentin-positive cells were encountered at the periphery of the islands suggesting an epithelial mesenchymal transition process. Analysis of the apical papilla revealed two novel histological regions; the periphery with dense and parallel aligned collagen type I defined as cortex fibrosa and the inner stromal tissue composed of less compacted collagen defined as medulla. FAPα expression was highly present within the medulla suggesting a role in extracellular matrix remodeling. Dental pulp tissue uncovered a heterogeneous FAPα staining but strong staining was noted within odontoblasts. In vitro studies confirmed the presence of FAPα expression in stem cells of the apical papilla and dental pulp. This study identified the expression of FAPα expression in dental stem cells which could open new perspectives in understanding dental root maturation and odontoblast function.

show abstract

Section: Discussionmentioning

confidence: 88%

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Driesen

Hilkens

Smisdom

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Previously, we showed that the tumor cells captured by CAM from blood expressed Epi (EPCAM/ EPCAM and CA125/ MUC16 ) and TP (CD44/ CD44 and seprase/ FAP ) cell surface proteins/ genes , as shown by gene expression and multiplex flow cytometric analyses on CAM-avid cells in blood of breast cancer patients [17]. EPCAM [26, 27]; CA125 [18, 28]; CD44 [29]; seprase [30–32] were potential biomarkers for subtypes of CTCs. To confirm these results, we used qRT-PCR assay to show that CAM-avid cells from blood samples of ovarian cancer (n=16) had significantly higher expression levels of the mRNAs of FAP (P-value<0.001), CD44 (P-value <0.001), MUC16 (P-value=0.001) and EPCAM (P-value=0.008) than that from healthy women (n=16) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2C–2G). The experimental spiking model involved spiking 1 to 1,000 invasive SB-MET human metastatic cells, originally described as LOX cells [32, 33], into 1-mL blood from a healthy donor as described [17–19]. The model was used to determine the analytical performance.…”

Section: Resultsmentioning

confidence: 99%

Treatment monitoring of patients with epithelial ovarian cancer using invasive circulating tumor cells (iCTCs)

Pearl

Dong

Tulley

et al. 2015

Gynecologic Oncology

Self Cite

View full text Add to dashboard Cite

Goals Contemporary management of epithelial ovarian cancer (EOC) uses biomarkers to monitor response to therapy. This study evaluates the role of invasive circulating tumor cells (iCTCs) in monitoring EOC treatment in comparison with serum cancer antigen 125 (CA125). Methods Molecular and microscopic analyses were used to identify seprase and CD44 as tumor progenitor (TP) markers. The iCTC flow cytometry assay was optimized using blood donated by 64 healthy donors, 49 patients with benign abdominal diseases and 123 EOC patients. Serial changes in iCTCs and CA125 were measured in 129 blood and 169 serum samples, respectively, from 31 EOC patients to assess their concordance during therapy and their relationship with risk of progressive disease (PD). Results The assay had 97% specificity and 83% sensitivity for detecting iCTCs in blood of EOC patients. iCTCs were detected in each monitoring patient (31/31, 100%) and in 110 of the 129 blood samples (85.3%). The concordance between changes in iCTCs / CA125 levels and changes in the intervals associated with no evidence of disease (NED) were markedly stronger (specificity: CA125 93.8%; iCTCs 90.6%), whereas increases in iCTCs (79.5%) were more sensitive than increases in CA125 (67.6%) to predict PD or relapse. Among the six patients who had greater than 6 measurements, iCTCs but not CA125 antedated changes in clinical status from PD to NED during and after chemotherapy, and predated relapse. Conclusion Serial measurements of iCTCs could predict therapeutic responsiveness in 31 EOC patients who underwent standard taxol / carboplatin therapy.

show abstract

“…For invasive melanoma cells, it has been shown that the TGF-β1-induced effect is mediated by Smad3/4. Treatment of metastatic cells with TGF-β1 causes a rapid and profound upregulation of endogenous seprase mRNA and an increase in binding of Smad3/4 to the seprase promoter in vivo 68 . Thus, the expression of collagen I and FAP upregulated by TGF-β1 seems to be mediated by the same signaling pathways.…”

Section: Single-chain Fragment For Fap Targetingmentioning

confidence: 99%

Immunoliposomes for Targeted Delivery of an Antifibrotic Drug

et al. 2015

View full text Add to dashboard Cite

Excessive extracellular matrix formation in organs and tissues arises from an imbalance between the synthesis and degradation of matrix proteins, especially collagen. This condition interferes with proper wound healing and regeneration, and to date, no specific treatment is available. In the present study, we propose a targeted drug delivery system consisting of cell-specific immunoliposomes (ILs) loaded with deferoxamine (DFO) as an antifibrotic drug. ILs were functionalized with polyethylene glycol (PEG) to improve the steric stability and prolong their half-life. In addition, a single-chain Fv (scFv) antibody fragment that specifically targets fibroblast activation protein (FAP) was incorporated. An in vitro fibrosis model was employed to test this construct. This model consisted of highly activated pro-fibrotic fibroblasts with 2- to 6-fold induction of selected fibrosis markers: cell/matrix deposited collagen I, total soluble collagen, and α smooth muscle actin. The activation was accompanied by a significant and cell-specific elevation of FAP expression and activity, thereby confirming that FAP is an adequate target for antifibrotic drug delivery. Purified anti-FAP scFv was shown to bind specifically to these cells without influencing the FAP enzymatic activity. DFO was demonstrated to have a dose-dependent antifibrotic activity as quantified by collagen deposition. Specific binding and intracellular uptake of DiI-labeled ILs into the activated fibroblasts were shown by flow cytometry and microscopy. Finally, DFO-loaded ILs targeted to FAP caused a significant reduction in the collagen deposition, whereas no effect was observed using liposomes that lacked the targeting antibody fragment. These results suggest that the FAP-specific scFv-conjugated liposomes have considerable potential for cell-specific targeting applicable as a therapy for excessive collagen deposition during fibrosis. In general, through liposome encapsulation, bioactive molecules, such as DFO, that have broad effects and poor cell penetration can be converted into cell-specific composites for targeted drug delivery.

show abstract

Transcriptional Regulation of Seprase in Invasive Melanoma Cells by Transforming Growth Factor-β Signaling

Cited by 29 publications

References 57 publications

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Treatment monitoring of patients with epithelial ovarian cancer using invasive circulating tumor cells (iCTCs)

Immunoliposomes for Targeted Delivery of an Antifibrotic Drug

Contact Info

Product

Resources

About