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Pancreatic stellate cells—role in pancreas cancer

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Abstract

Background

Adenocarcinomas of the pancreas are characterized by a rapid progression, an early metastasis, a limited response to chemo- and radiotherapy, and an intense fibrotic reaction known as tumor desmoplasia. Carcinoma cells are surrounded by a dense stroma consisting of myofibroblast-like cells, collagens, and fibronectin.

Materials and methods

This review describes the interaction of activated pancreatic stellate cells (myofibroblast-like cells) with tumor cells in pancreas adenocarcinomas. Our data were obtained in cell culture experiments and in in vivo investigations.

Results

Carcinoma cells produce soluble mediators and stimulate motility, proliferation, matrix-, and MMP synthesis of stellate cells. Vice versa-activated stellate cells release mitogens, stimulating proliferation of cancer cells. Cancer cell proliferation and resistance to apoptosis might further be induced by the microenvironment (extracellular matrix), which is primarily provided by stellate cells. A very important aspect in the interaction of stellate cells with cancer cells is the expression of EMMPRIN (extracellular matrix metalloproteinase inducer) by cancer cells, the shedding of the extracellular part of EMMPRIN by matrix metalloproteinases (MMPs), and the induction of MMPs in stellate cells by soluble EMMPRIN. In particular, the stellate cells in close proximity to tumor cells therefore express MMPs and degrade connective tissue.

Conclusion

Through complex interactions between stellate cells and carcinoma cells, tumor progression and cancer cell invasion are accelerated. As we gain better understanding of these mechanisms, adequate therapies to reduce tumor cell invasion and cancer progression might be developed.

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Abbreviations

DMEM:

Dulbecco’s modification of Eagle’s medium

ECM:

extracellular matrix

FAK:

focal adhesion kinase

FCS:

fetal calf serum

FN:

fibronectin

PDAC:

pancreas ductal adenocarcinoma

PDGF:

platelet-derived growth factor

PSC:

pancreatic stellate cells

SMA:

α-smooth muscle actin

SN:

culture supernatant

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Authors and Affiliations

  1. Department Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany

    Max G. Bachem, Shaoxia Zhou, Karin Buck & Wilhelm Schneiderhan

  2. Department of Surgery, Ostalbklinikum Aalen, Aalen, Germany

    Marco Siech

  3. ZE Klinische Chemie, Universität Ulm-Klinikum, Robert-Kochstrasse 9, 89070, Ulm, Germany

    Max G. Bachem

Authors
  1. Max G. Bachem
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  2. Shaoxia Zhou
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  3. Karin Buck
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  4. Wilhelm Schneiderhan
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  5. Marco Siech
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Corresponding author

Correspondence to Max G. Bachem.

Additional information

Grant support: Deutsche Forschungsgemeinschaft (SFB 518, project A7 to M.G.B. and WS).

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Bachem, M.G., Zhou, S., Buck, K. et al. Pancreatic stellate cells—role in pancreas cancer. Langenbecks Arch Surg 393, 891–900 (2008). https://doi.org/10.1007/s00423-008-0279-5

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  • DOI: https://doi.org/10.1007/s00423-008-0279-5

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