Pancreatic stellate cells--role in pancreas cancer.
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.


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.


CONCLUSIONS
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.
Bachem
Max G
MG
Department Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany. max.bachem@uniklinik-ulm.de
Zhou
Shaoxia
S
Buck
Karin
K
Schneiderhan
Wilhelm
W
Siech
Marco
M
D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D051926:Basigin / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000473:pathology / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D011230:Precancerous Conditions / Q000473:pathology / Q000503:physiopathology
C497886:BSG protein, human; D051926:Basigin; D003094:Collagen