Inflammation and Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fighting Against Multiple Opponents

Khalafalla, Farid G.; Khan, Mohammad W.

doi:10.1177/1179064417709287

Cited by 31 publications

(20 citation statements)

References 225 publications

(415 reference statements)

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“…After 24 h of preculture followed by 24 h of serum starvation, both KPC2 and eKIC dT-MOC platforms were treated with 1.0 × 10 −9 m transforming growth factor-beta1 (TGF-β1) for up to 48 h. We chose to treat cells with TGF-β1 because TGF-β/SMAD is a well characterized signaling pathway that induces EMT in a number of cancers, including PDAC, often leading to metastasis, invasion, and chemoresistance. [35][36][37] EMT is modulated by complex regulatory networks involving a number of EMTinducing transcription factors (SNAIL, ZEB, and TWIST) as well as other transcriptional regulators through epigenetic modifications and microRNAs (miRNAs). The micrographs of TGF-β1 treated groups showed notably enhanced sprouts and local invasion for both KPC2 and eKIC cell genotypes ( Figure 6A).…”

Section: Local Invasion Of Cancer Cellsmentioning

confidence: 99%

A Biomimetic Tumor Model of Heterogeneous Invasion in Pancreatic Ductal Adenocarcinoma

Bradney

Venis

Yang

et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) is a complex, heterogeneous, and genetically unstable disease. Its tumor microenvironment (TME) is complicated by heterogeneous cancer cell populations and strong desmoplastic stroma. This complex and heterogeneous environment makes it challenging to discover and validate unique therapeutic targets. Reliable and relevant in vitro PDAC tumor models can significantly advance the understanding of the PDAC TME and may enable the discovery and validation of novel drug targets. In this study, an engineered tumor model is developed to mimic the PDAC TME. This biomimetic model, named ductal tumor‐microenvironment‐on‐chip (dT‐MOC), permits analysis and experimentation on the epithelial–mesenchymal transition (EMT) and local invasion with intratumoral heterogeneity. This dT‐MOC is a microfluidic platform where a duct of murine genetically engineered pancreatic cancer cells is embedded within a collagen matrix. The cancer cells used carry two of the three mutations of KRAS, CDKN2A, and TP53, which are key driver mutations of human PDAC. The intratumoral heterogeneity is mimicked by co‐culturing these cancer cells. Using the dT‐MOC model, heterogeneous invasion characteristics, and response to transforming growth factor‐beta1 are studied. A mechanism of EMT and local invasion caused by the interaction between heterogeneous cancer cell populations is proposed.

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Section: Local Invasion Of Cancer Cellsmentioning

confidence: 99%

A Biomimetic Tumor Model of Heterogeneous Invasion in Pancreatic Ductal Adenocarcinoma

Bradney

Venis

Yang

et al. 2020

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“…Several transcription factors, such as Snai1, Slug and Twist1, are involved in activating EMT programs in pancreatic cancer [ 48 ]. According to recent data, inflammation is a major driver of EMT in pancreatic cancer cells [ 49 ]. While EMT promotes dissemination of cancer cells, it has also been found that metastases show an epithelial histology.…”

Section: The Microenvironmentmentioning

confidence: 99%

Pancreatic cancer: disease dynamics, tumor biology and the role of the microenvironment

et al. 2018

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Pancreatic cancer is known for its propensity to metastasize. Recent studies have challenged the commonly held belief that pancreatic cancer is a stepwise process, where tumor cells disseminate late in primary tumor development. Instead it has been suggested that pancreatic tumor cells may disseminate early and develop independently and in parallel to the primary tumor. Circulating tumor cells can be found in most patients with pancreatic cancer, even in those with localized stage. Also, recent phylogenetic analyses have revealed evidence for a branched evolution where metastatic lineages can develop early in tumor development. In this Review, we discuss current models of pancreatic cancer progression and the importance of the tumor microenvironment, in order to better understand the recalcitrant nature of this disease.

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“…Pancreatic ductal adenocarcinoma (PDA) is associated with very high mortality rate with no effective therapy options. PDA is also characterized with inflammatory and immunosuppressive tumor microenvironments ( 119 – 121 ). Daley et al found that NLRP3 deletion was protective against PDA ( 118 ).…”

Section: Introductionmentioning

confidence: 99%

Inflammasomes and Cancer: The Dynamic Role of the Inflammasome in Tumor Development

2017

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Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer. However, very recent studies demonstrate that inflammasomes promote tumor progression in skin and breast cancer. These results indicate that inflammasomes can promote and suppress tumor development depending on types of tumors, specific inflammasomes involved, and downstream effector molecules. The complicated role of inflammasomes raises new opportunities and challenges to manipulate inflammasome pathways in the treatment of cancer.

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Inflammation and Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fighting Against Multiple Opponents

Cited by 31 publications

References 225 publications

A Biomimetic Tumor Model of Heterogeneous Invasion in Pancreatic Ductal Adenocarcinoma

A Biomimetic Tumor Model of Heterogeneous Invasion in Pancreatic Ductal Adenocarcinoma

Pancreatic cancer: disease dynamics, tumor biology and the role of the microenvironment

Inflammasomes and Cancer: The Dynamic Role of the Inflammasome in Tumor Development

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