StellaTUM: Consensus criteria on pancreatic stellate cells

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer related deaths in western societies. One of the unique features of pancreatic ductal adenocarcinoma is the excessive stromal/fibrotic tissue reaction which forms approximately 80% of the tumor mass whereas cancer cells themselves form ~20%. This abundant stromal tissue is believed to contribute to the progression and chemo-/radio-resistance of this aggressive cancer. A similar stromal reaction is also a characteristic feature of chronic pancreatitis.

Recent studies have shown that the stromal component of the tumor mass impacts on the survival of the patients more than the lymph-node status of the cancer. The mechanisms behind this important phenomenon are currently being scrutinized. For example it has been shown that the tumor stromal interactions support tumor growth in vitro and in animal models and provide chemoresistance. Similarly tumor-stromal interactions inhibit angiogenesis in pancreatic cancer and possibly contribute to the metastatic tumor spread. In a recent mouse model it has also been shown that inhibition of the hedgehog signalling pathway in the stroma temporarily increases the chemoresponsiveness of pancreatic cancer cells.

The cells responsible for producing the stromal reaction in pancreatic cancer and chronic pancreatitis are pancreatic stellate cells (PSCs, the key fibrogenic cells in the pancreas). Pancreatic stellate cells are activated myofibroblasts-like cells of the pancreas. Although similar cells were first identified in the liver in 1870, the identification and routine cultivation of PSC was only first described in 1998. In 1998 two independent research groups from Germany (Prof. Bachem et al.) and from Australia (Prof. Apte et al.) made the initial steps by isolating pancreatic stellate cells that today appear as a promising novel therapeutic target to reduce pancreatic tumour growth and metastasis and resistance to therapy. In addition, they may also be a target for depletion of fibrosis in chronic pancreatitis.

 

As of today several research groups all around the world are focusing on PSC biology as it relates to pancreatic cancer and chronic pancreatitis. Judging by “Thomson Web of Science” “Pancreatic stellate cells” have an h-index of 36 with 60 publications and 1200 citations in 2010

 

Despite exponentially increasing data, the methods for studying the PSC remain variable. Although within individual laboratories methods are consistent, different methodologies used by various research groups makes it difficult to compare results and conclusions.  Several layers of complexity is added due to following reasons

  1. Usage of different sources for stellate cell extraction such as rat, mouse or human pancreas.
  2. Usage of various tissues such as normal pancreas, chronic pancreatitis and pancreatic cancer, which exhibit significantly different genetic profiles.
  3. Mixed origins of stellate cells such as bone-marrow, conversion from local fibroblasts or generation from epithelial cells through epithelial-to-mesenchymal transformation.

The Pancreatic Star Alliance will hold its first meeting on the 4th of March 2011 in Munich, Germany. The aim of this meeting is to standardize the tools available for pancreatic stellate cell research at a relatively early stage to prevent future confusion. In order to increase the translational capacity of the research in the field, it is imperative that consensus criteria are defined on PSC cultivation, usage and reporting of results. Moreover, Pancreatic Star Alliance will provide a platform both for the opinion leaders as well as for the researchers working on bench with stellate cells.

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