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Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

Morvaridi S, Dhall D, Greene MI, Pandol SJ, Wang Q - Sci Rep (2015)

Bottom Line: Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells.In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues.Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, CA 90048.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic and inflammatory microenvironment that is formed primarily by activated, myofibroblast-like, stellate cells. Although the stellate cells are thought to contribute to tumorigenesis, metastasis and drug resistance of PDAC, the signaling events involved in activation of the stellate cells are not well defined. Functioning as transcription co-factors, Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) modulate the expression of genes involved in various aspects of cellular functions, such as proliferation and mobility. Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells. In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues. Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice. These findings indicate that YAP and TAZ may play a critical role in modulating pancreatic tissue regeneration, neoplastic transformation, and stellate cell functions in both PDAC and pancreatitis.

No MeSH data available.


Related in: MedlinePlus

Immunofluorescence analysis of YAP in stellate cells of human PDAC tissues.(A) YAP (red) and α-SMA (green), and DAPI (blue). Note that YAP can be detected in both the cancer cells and the stromal cells. Magnification: 20 x. (B) Image of PDAC tissue stained in the same way as in (A), showing a field predominantly of stellate cells. Magnification: 63x.
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f6: Immunofluorescence analysis of YAP in stellate cells of human PDAC tissues.(A) YAP (red) and α-SMA (green), and DAPI (blue). Note that YAP can be detected in both the cancer cells and the stromal cells. Magnification: 20 x. (B) Image of PDAC tissue stained in the same way as in (A), showing a field predominantly of stellate cells. Magnification: 63x.

Mentions: We noted that, in both chronic pancreatitis and pancreatic cancer tissues, the stromal cells stained positive for YAP and TAZ show morphology of stellate cells, which are characterized by elongated nuclei and branching cell body (Figs 3,4 and 5; Supplemental Figures 2 and 3). By immunofluorescence, we found that YAP can be detected in the same set of cells that are stained positive for α-SMA, a marker for activated stellate cells. While α-SMA is localized to the cytoplasm in these cells, YAP can be found in both the nuclei and the cytoplasm (Figs 6 and 7). Thus, our results indicate that YAP is expressed in the stellate cells of both chronic pancreatitis and PDAC. Interestingly, ANXA2 is co-expressed with YAP in activated stellate cells (Fig. 7) and in cancer cells (Fig. 8).


Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

Morvaridi S, Dhall D, Greene MI, Pandol SJ, Wang Q - Sci Rep (2015)

Immunofluorescence analysis of YAP in stellate cells of human PDAC tissues.(A) YAP (red) and α-SMA (green), and DAPI (blue). Note that YAP can be detected in both the cancer cells and the stromal cells. Magnification: 20 x. (B) Image of PDAC tissue stained in the same way as in (A), showing a field predominantly of stellate cells. Magnification: 63x.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645184&req=5

f6: Immunofluorescence analysis of YAP in stellate cells of human PDAC tissues.(A) YAP (red) and α-SMA (green), and DAPI (blue). Note that YAP can be detected in both the cancer cells and the stromal cells. Magnification: 20 x. (B) Image of PDAC tissue stained in the same way as in (A), showing a field predominantly of stellate cells. Magnification: 63x.
Mentions: We noted that, in both chronic pancreatitis and pancreatic cancer tissues, the stromal cells stained positive for YAP and TAZ show morphology of stellate cells, which are characterized by elongated nuclei and branching cell body (Figs 3,4 and 5; Supplemental Figures 2 and 3). By immunofluorescence, we found that YAP can be detected in the same set of cells that are stained positive for α-SMA, a marker for activated stellate cells. While α-SMA is localized to the cytoplasm in these cells, YAP can be found in both the nuclei and the cytoplasm (Figs 6 and 7). Thus, our results indicate that YAP is expressed in the stellate cells of both chronic pancreatitis and PDAC. Interestingly, ANXA2 is co-expressed with YAP in activated stellate cells (Fig. 7) and in cancer cells (Fig. 8).

Bottom Line: Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells.In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues.Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, CA 90048.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic and inflammatory microenvironment that is formed primarily by activated, myofibroblast-like, stellate cells. Although the stellate cells are thought to contribute to tumorigenesis, metastasis and drug resistance of PDAC, the signaling events involved in activation of the stellate cells are not well defined. Functioning as transcription co-factors, Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) modulate the expression of genes involved in various aspects of cellular functions, such as proliferation and mobility. Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells. In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues. Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice. These findings indicate that YAP and TAZ may play a critical role in modulating pancreatic tissue regeneration, neoplastic transformation, and stellate cell functions in both PDAC and pancreatitis.

No MeSH data available.


Related in: MedlinePlus