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Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

Karamitopoulou E - Front Oncol (2013)

Bottom Line: Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling.Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT).Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pathology Division, Institute of Pathology, University of Bern Bern, Switzerland.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

No MeSH data available.


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Possible interactions of tumor budding cells, EMT-type cells, and CSCs.
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Figure 2: Possible interactions of tumor budding cells, EMT-type cells, and CSCs.

Mentions: Tumor budding is thought to reflect the process of EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals (Guarino et al., 2007; Katoh, 2011). Additionally, it has been suggested that tumor budding cell may have a “stem cell” character. Possible interactions of tumor budding cells, EMT-type cells, and CSCs are shown in Figure 2. The WNT pathway which is involved in the process of tumor budding has a strong association with CSCs and the development of a stem cell-like phenotype (Katoh, 2011). Moreover, emerging evidence has shown that CSCs share similar molecular characteristics with EMT-type cells, are drug resistant and have higher metastatic potential (Mani et al., 2008; Morel et al., 2008). In an excellent recent work by Floor et al. (2011) similarities between CSCs and EMT-cells were further explored. It was shown that cancer cells in EMT, that is, EMT-cells, share many properties with the classical so-called “CSC”s. In fact, there are many indications that CSCs present characteristics of EMT-cells and conversely that EMT-cells acquire properties of CSCs, including expression of the markers CD44/CD24, dormancy etc., and vice-versa. The overlap of CSC- and EMT-properties has been also extensively discussed in many recent publications (Alexander et al., 2008; Tomaskovic-Crook et al., 2009; Singh and Settleman, 2010).


Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

Karamitopoulou E - Front Oncol (2013)

Possible interactions of tumor budding cells, EMT-type cells, and CSCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539658&req=5

Figure 2: Possible interactions of tumor budding cells, EMT-type cells, and CSCs.
Mentions: Tumor budding is thought to reflect the process of EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals (Guarino et al., 2007; Katoh, 2011). Additionally, it has been suggested that tumor budding cell may have a “stem cell” character. Possible interactions of tumor budding cells, EMT-type cells, and CSCs are shown in Figure 2. The WNT pathway which is involved in the process of tumor budding has a strong association with CSCs and the development of a stem cell-like phenotype (Katoh, 2011). Moreover, emerging evidence has shown that CSCs share similar molecular characteristics with EMT-type cells, are drug resistant and have higher metastatic potential (Mani et al., 2008; Morel et al., 2008). In an excellent recent work by Floor et al. (2011) similarities between CSCs and EMT-cells were further explored. It was shown that cancer cells in EMT, that is, EMT-cells, share many properties with the classical so-called “CSC”s. In fact, there are many indications that CSCs present characteristics of EMT-cells and conversely that EMT-cells acquire properties of CSCs, including expression of the markers CD44/CD24, dormancy etc., and vice-versa. The overlap of CSC- and EMT-properties has been also extensively discussed in many recent publications (Alexander et al., 2008; Tomaskovic-Crook et al., 2009; Singh and Settleman, 2010).

Bottom Line: Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling.Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT).Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pathology Division, Institute of Pathology, University of Bern Bern, Switzerland.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

No MeSH data available.


Related in: MedlinePlus