Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications.
OBJECTIVE
Since the discovery of cancer cells with stem-like characteristics in hematopoietic malignancies and, more recently, in solid tumors, enormous attention has been paid to the stem-cell nature of pancreatic cancer. Among the most important properties of cancer stem cells their high capacity for tumorigenicity as well as their ability to metastasize is under special research interest today.


METHODS
Here, we give a brief overview of main components used to confirm the stem-cell-like behavior of putative cancer stem cells and discuss markers and methods for identifying them in pancreatic cancer. Finally, the review provides some new suggestions as to how specifically target these cells and improve current therapy regimens.


RESULTS
The cancer stem-cell hypothesis is a fundamentally different model of carcinogenesis composed of two separate but dependent on each other characteristics of stem cells--aberrant activation of their tightly regulated processes of self-renewal and differentiation and their resistance towards chemo- and radiotherapy. The cancer stem cells may further be identified based on their expression of cell surface markers or their functional characteristics. The concept of molecular targeting of such highly tumorigenic cancer cells aimed to sensitize tumors toward conventional therapies and effectively abrogate tumor growth and metastasis.


CONCLUSIONS
The presence of cancer stem cells in pancreatic tumors has prognostic relevance and influences therapeutic response. Evidence suggests that metastatic potential may be conferred to these highly tumorigenic cells as well. A better understanding of the biological behavior of these cells may further improve therapeutic approaches and outcomes in patients with this devastating disease.
Ischenko
Ivan
I
Department of Surgery, Grosshadern Campus, Medical Center of the University of Munich, Marchioninistr. 15, Munich, 81377, Germany. Ivan.Ischenko@med.uni-muenchen.de
Seeliger
Hendrik
H
Kleespies
Axel
A
Angele
Martin K
MK
Eichhorn
Martin E
ME
Jauch
Karl-Walter
KW
Bruns
Christiane J
CJ
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015197:Carcinogenicity Tests; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor