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Pancreatic Stellate Cells: Partners in Crime with Pancreatic Cancer Cells

¹ Pancreatic Research Group, South Western Sydney Clinical School, and School of Medical Sciences/Pathology, and ² Oncology Unit, Prince of Wales Hospital, Sydney, Australia

Requests for reprints: Minoti V. Apte, Pancreatic Research Group, South Western Sydney Clinical School, Room 505, Level 5, Wallace Wurth Building, The University of New South Wales, Sydney, New South Wales 2052, Australia. Phone: 61-2-9385-8273; Fax: 61-2-9385-1389; E-mail: m.apte{at}unsw.edu.au.

Key Words: Pancreatic cancer • Cellular, molecular, and tumor biology • Tumor-stromal cell interactions • Cell-cell interactions • Tumor progression, invasion, and metastasis

Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection of saline, hPSCs, MiaPaCa-2 cells, or hPSCs + MiaPaCa-2. After 7 weeks, tumor size, metastases, and tumor histology were assessed. In vitro studies assessed the effect of cancer cell secretions on PSC migration and the effect of hPSC secretions on cancer cell proliferation, apoptosis, and migration. Possible mediators of the effects of hPSC secretions on cancer cell proliferation were examined using neutralizing antibodies. Compared with mice receiving MiaPaCa-2 cells alone, mice injected with hPSCs + MiaPaCa-2 exhibited (a) increased tumor size and regional and distant metastasis, (b) fibrotic bands (desmoplasia) containing activated PSCs within tumors, and (c) increased tumor cell numbers. In vitro studies showed that, in the presence of pancreatic cancer cells, PSC migration was significantly increased. Furthermore, hPSC secretions induced the proliferation and migration, but inhibited the apoptosis, of MiaPaCa-2 and Panc-1 cells. The proliferative effect of hPSC secretions on pancreatic cancer cells was inhibited in the presence of neutralizing antibody to platelet-derived growth factor. Our studies indicate a significant interaction between pancreatic cancer cells and stromal cells (PSCs) and imply that pancreatic cancer cells recruit stromal cells to establish an environment that promotes cancer progression. [Cancer Res 2008;68(7):2085–93]

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