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• W3142189795 abstract "Pancreatic stellate cells (PSCs) within the tumor microenvironment are important for cancer cell growth, migration and metastasis. We have shown previously that the lipid signaling molecule sphingosine 1-phosphate (S1P) activates PSCs to release paracrine factors including MMP9 to promote tumor cell migration and invasion in vitro through a S1P receptor-2 (SIP2)-c-abl-NFκB-MMP9 pathway. We therefore hypothesized that knockdown of S1P2 in PSCs might inhibit tumor growth in vivo. Methods: We used subcutaneous and orthotopic tumor cell/PSC co-implantation models in which PSC are known to stimulate tumor growth in vivo. In the subcutaneous model, L3.6 human pancreatic cancer cells were mixed with human PSCs transfected with control or S1P2 shRNA (1:1 ratio) and subcutaneously injected into the lower flank of nude mice. Tumor diameters were measured and tumor tissues were cryosectioned for immunofluorescence studies and mRNA was extracted for real time qPCR analyses. Orthotopic pancreatic implant models were done with ASPC1 cell mixed with PSC transfected with scramble or S1P2 shRNA PSC (1: 1 ratio) injected into the pancreatic tail of nude mice. Tumor size was monitored with in vivo Luciferase activity. Results: Tumor size was smaller in L3.6 derived tumors that were coimplanted with S1P2 shRNA PSC compared to scramble PSC (64 mg vs 145 mg, n=10, p<0.01). qPCR from tumor tissue from S1P2sh PSC and L3.6 co-implantation showed a 34% reduction of MMP9 and 26% reduction of CSF1r mRNA levels compared to control (n= 10, p<0.05). Staining for endothelial cell marker Von Willebrand factor indicated decreased angiogenesis in the tumor from co-implantation of S1P2sh PSC and L3.6 compare to control PSC and L3.6 co-implantation. Similar results were observed in the orthotopic model using ASPC1 cells. Conclusion: S1P2 in PSCs promotes cancer growth in vivo through activation of the tumor microenvironment including angiogenesis and macrophage infiltration." @default.
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• W3142189795 date "2014-01-01" @default.
• W3142189795 modified "2023-10-17" @default.
• W3142189795 title "Tu1907 Differences in Characteristics and Tumor Biology of Ampullary Adenomas in Patients With FAP and Sporadic Adenomas" @default.
• W3142189795 hasPublicationYear "2014" @default.
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