Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications

Abstract

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.

Gastric tumor-initiating CD44+ cells and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT

“…DAPT treatment inhibited the expression of Notch1 signaling pathway members and its downstream target Hes1, which reduced Snail expression and impaired EMT in CD44 + cells: These results were in accordance with other previous studies (28,29). It has been proposed that transformed epithelial cells may activate embryonic programs for epithelial plasticity and switch from sessile and epithelial phenotypes to motile and mesenchymal phenotypes (30).…”

Bmi-1 Promotes the Chemoresistance, Invasion and Tumorigenesis of Pancreatic Cancer Cells

“…CD44+CD24+ESA+ pancreatic CSCs which possess tumorigenic potential have been isolated [4]. Several developmental signaling pathways, such as the hedgehog, have been shown to be aberrantly activated and play important roles in regulating the self-renewal of CSCs [5,6]. Moreover, abnormal activation of such signaling pathways are crucially involved in tumorigenesis [7].…”

Targeting the vasculature of visceral tumors: novel insights and treatment perspectives

“…So far, clinical development of targeted agents directed against validated pathways like EGFR, the mutant KRAS protein and VEGF-mediated angiogenesis as monotherapy or in combination with gemcitabine has been disappointing. Therefore, relatively unexplored signaling pathways, for example the presence of cancer stem cells as mentioned below, offer great promise to increase the understanding of the complex molecular biology and pathways in advanced pancreatic cancer [75,76]. In addition, novel tumor vascular targeting strategies by cationic liposomes in combination with standard gemcitabine chemotherapy can further improve therapeutic efficacy.…”

“…First observed by Dick et al, these cells own typical stem cell characteristics: They possess the ability to self-renewal and produce more differentiated cells without stem cell properties [77]. The cancer stem cell hypothesis provides a smart explanation for the limitation of many current cancer models and suggests new understanding of carcinogenesis in tumor tissue [76,78]. Moreover, novel therapeutic approaches and treatment strategies for cancer therapy may be discovered and established in the near future.…”

“…At first, tumor cells originate from tissue stem or progenitor cells through the deregulation of the tightly regulated process of self-renewal [79]. Consequently, CSCs are defined as cancer cells with the ability to divide into new malignant stem cells and daughter cells that differentiate and give rise to the heterogenous tumor cell mass [76].…”