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...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.3960-3960
Hauptverfasser: Bharadwaj, Uddalak, Marin-Muller, Christian, Zhang, Yu-Qing, Li, Min, Chen, Changyi, Yao, Qizhi
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Sprache:eng
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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