S1821 Differential Effects of a Protein Free Diet and Amino Acid Infusion On Pancreatic Growth and Digestive Enzyme Expression

The desmoplastic/stromal reaction in pancreatic cancer plays a critical role in tumour growth and metastasis. The key cells responsible for this fibrous reaction in pancreatic cancer are pancreatic stellate cells (PSCs). We have shown a bi-directional interaction between PSCs and cancer cells which facilitates cancer progression. Growth factors and cytokines produced by tumour cells activate PSCs (increased proliferation, migration and synthesis of extracellular matrix [ECM] proteins). We propose a role for heat shock proteins (HSPs) in these processes. HSPs are a family of chaperone proteins known to play a role in cellular functions such as apoptosis, migration and ECM modulation. We have shown that PSCs express HSP 27, 47, 70 and 90. However, little is known about their role in PSC functions. Aim: To determine whether HSP expression within PSCs is influenced by PSC activation. Methods: PSCs were isolated from pancreatic tissue resected from patients with benign pancreatic diseases (normal PSCs) and pancreatic ductal adenocarcinoma (cancer-associated, CA-PSCs). CA-PSCs were exposed to PDGF and TGFβ for 24h. HSP levels in PSCs and human pancreatic cancer cells (MiaPaCa-2, Panc1, ASPC-1) were assessed by western blotting (densitometry units, mean±SE). Results: CA-PSCs exhibited higher HSP levels compared to normal PSCs (Table). CA-PSCs also exhibited increased HSP27 and HSP47 expression compared to pancreatic cancer cells (Table). Treatment of CA-PSCs with PDGF induced HSPs (% of control data: HSP27 389±121*, HSP47 158±9*, HSP70 220±25*, HSP90 228±29*; *p<0.05). PSCs treated with TGFβ had increased HSP47 levels (152±12*, *p<0.05). Conclusions: i) CAPSCs exhibit increased HSP levels compared to normal PSCs and higher HSP27 and HSP47 levels compared to pancreatic cancer cells; and ii) HSP expression is increased in PSCs exposed to activating factors. Modulation of HSPs in PSCs may alter their function and how they interact with cancer cells.