Abstract 3960: Mesothelin overexpression promotes autocrine IL-6/sIL-6R trans-signaling to stimulate pancreatic cancer cell proliferation
Background: We have shown previously that mesothelin (MSLN) overexpression in pancreatic cancer (PC) cells leads to enhanced cell survival/proliferation in vitro & tumor progression in a xenograft mouse model. The objective of this study is to determine the underlying MSLN-induced growth factors...
Gespeichert in:
Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.3960-3960 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Background: We have shown previously that mesothelin (MSLN) overexpression in pancreatic cancer (PC) cells leads to enhanced cell survival/proliferation in vitro & tumor progression in a xenograft mouse model. The objective of this study is to determine the underlying MSLN-induced growth factors/signaling that contribute to the PC cell proliferation.
Methods: PC tissue/serum & cell lines were used to evaluate MSLN/IL-6 expression. MIA PaCa-2 & Panc1 cells stably over-expressing MSLN (MIA-MSLN, Panc1-MSLN) & vector control cell lines (MIA-V, Panc1-V) were generated by using retrovirus expression system. IL-6 was measured by BioPlex. Silencing of MSLN/IL-6 was done by using specific siRNAs. NF-κB activation was examined by western blot & reporter assay. Different forms of IL-6Rs were determined by western blot, real-time PCR & FACS. Cell proliferation was measured by MTT. Cell cycle analysis was performed using PI staining & apoptosis determination by caspase3 cleavage.
Results and Conclusions: MSLN expression positively correlated with secreted IL-6 in a panel of human PC specimens (serum) & cell lines (supernatants). Both MIA-MSLN & Panc1-MSLN showed high IL-6 expression & siRNA silencing of MSLN significantly reduced the IL-6 level (p |
---|---|
ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/1538-7445.AM10-3960 |