scholarly journals Pancreatic stellate cells activated by mutant KRAS-mediated PAI-1 upregulation foster pancreatic cancer progression via IL-8

Theranostics ◽  
2019 ◽  
Vol 9 (24) ◽  
pp. 7168-7183 ◽  
Author(s):  
Hao-Chen Wang ◽  
Yung-Lun Lin ◽  
Ching-Cheng Hsu ◽  
Ying-Jui Chao ◽  
Ya-Chin Hou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Pai 1

Sa1453 Kindlin-2/FERMT2 in Pancreatic Stellate Cells Promotes Pancreatic Cancer Progression

2016 ◽  
Vol 150 (4) ◽  
pp. S319
Author(s):  
Naoki Yoshida ◽  
Atsushi Masamune ◽  
Shin Hamada ◽  
Eriko Nakano ◽  
Kazuhiro Kikuta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells

Pancreatic stellate cells: Aiding and abetting pancreatic cancer progression

Pancreatology ◽  
2020 ◽  
Vol 20 (3) ◽  
pp. 409-418 ◽  
Author(s):  
Srinivasa P. Pothula ◽  
Romano C. Pirola ◽  
Jeremy S. Wilson ◽  
Minoti V. Apte
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells

scholarly journals Autophagy Is Required for Activation of Pancreatic Stellate Cells, Associated With Pancreatic Cancer Progression and Promotes Growth of Pancreatic Tumors in Mice

2017 ◽  
Vol 152 (6) ◽  
pp. 1492-1506.e24 ◽  
Author(s):  
Sho Endo ◽  
Kohei Nakata ◽  
Kenoki Ohuchida ◽  
Shin Takesue ◽  
Hiromichi Nakayama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Pancreatic Tumors

scholarly journals Cav-1 Ablation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Growth through Nrf2-Induced shh Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shan Shao ◽  
Tao Qin ◽  
Weikun Qian ◽  
Xuqi Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Shh Signaling ◽  
Patient Response ◽  
Shh Pathway ◽  
Pancreatic Cancer Cells ◽  
Signaling Activation

A more comprehensive understanding of the complexity of pancreatic cancer pathobiology, especially, and understanding of the role of the tumor microenvironment (TME) in disease progression should pave the way for therapies to improve patient response rates. Previous studies reported that caveolin-1 (Cav-1) has both tumor-promoting and tumor-suppressive functions. However, the function of Cav-1 in the pancreatic cancer microenvironment remains largely unexplored. Here, we show that coinjection of Cav-1-silenced pancreatic stellate cells (PSCs) with pancreatic cancer cells increased tumor growth. To comprehensively characterize paracrine communication between pancreatic cancer cells and PSCs, PSCs were cultured with pancreatic cancer cell conditioned medium (CM) containing cytokines. We reveal that Cav-1-silenced PSCs facilitated the growth of pancreatic cancer cells via enhanced paracrine shh/MMP2/bFGF/IL-6 signaling. Specifically, Cav-1-silenced PSCs exhibited increased shh expression, which heterotypically activated the shh signaling pathway in pancreatic cancer cells. Moreover, Cav-1-deficient PSCs accumulated ROS to enhance the shh pathway and angiogenesis in pancreatic cancer cells. In addition, overexpression of Nrf2 reversed the effects of Cav-1 knockdown on PSCs, increasing ROS production and enhancing paracrine shh/MMP2/bFGF/IL-6 signaling. Together, our findings show that stromal Cav-1 may mediate different mechanisms in the complex interaction between cancer cells and their microenvironment though Nrf2-induced shh signaling activation during pancreatic cancer progression.

Nrf2 expression in pancreatic stellate cells promotes progression of cancer

2021 ◽  
Author(s):  
Yu Tanaka ◽  
Shin Hamada ◽  
Ryotaro Matsumoto ◽  
Keiko Taguchi ◽  
Masayuki Yamamoto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Smooth Muscle Actin ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Immunodeficient Mice ◽  
Pancreatic Cancer Cells ◽  
Nrf2 Target Gene ◽  
Migration Capacity

It was previously identified that systemic Nrf2-deletion attenuates pancreatic cancer progression in a mutant K-ras/p53-expressing mouse model (KPC mouse). In this study, the type of cell that is responsible for the retarded cancer progression was elucidated. Human pancreatic cancers were first examined, and elevated expression of NRF2-target gene products in a-smooth muscle actin-positive cells was found, suggesting that pancreatic stellate cells (PSCs) are involved in this process. Closer examination of primary cultured PSCs from Nrf2-deleted mice revealed that the cells were less proliferative and retained a lower migration capacity. The conditioned medium of Nrf2-deleted PSCs exhibited reduced growth-stimulating effects in pancreatic cancer cells. KPC mouse-derived pancreatic cancer cells co-injected with wild-type PSCs developed significantly larger subcutaneous tumors in immunodeficient mice than those co-injected with Nrf2-deleted PSCs. These results demonstrate that Nrf2 actively contributes to the function of PSCs to sustain KPC cancer progression, thus, suggesting that Nrf2 inhibition in PSCs may be therapeutically important in pancreatic cancer.

scholarly journals Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 901
Author(s):  
Ramiz S. Ahmad ◽  
Timothy D. Eubank ◽  
Slawomir Lukomski ◽  
Brian A. Boone
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Cellular Mechanisms ◽  
Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

scholarly journals Multifunctional role of pancreatic stellate cells in pancreatic cancer

2019 ◽  
Vol 2 ◽  
pp. 10-10 ◽  
Author(s):  
Alpha R. Mekapogu ◽  
Srinivasa P. Pothula ◽  
Romano C. Pirola ◽  
Jeremy S. Wilson ◽  
Minoti V. Apte
Keyword(s):  
Pancreatic Cancer ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells
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