A 3-Dimensional Coculture Model to Visualize and Monitor Interaction Between Pancreatic Cancer and Islet β Cells

Pancreas ◽  
2021 ◽  
Vol 50 (7) ◽  
pp. 982-989
Author(s):  
Sandeep Kumar ◽  
Daria Jach ◽  
Wendy Macfarlane ◽  
Tatjana Crnogorac-Jurcevic
Keyword(s):  
Pancreatic Cancer ◽  
Β Cells ◽  
3 Dimensional ◽  
Coculture Model

PNU-74654 enhanced the antiproliferative activity of gemcitabine via targeting Wnt/β-catenin Pathway in Pancreatic cancer

2021 ◽  
Author(s):  
Sajjad Sharifi ◽  
Farzad Rahmani ◽  
Abolfazl Nosrati-Tirkani ◽  
Shima Mehrabadi ◽  
Hamid Fiuji ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Culture ◽  
Wnt Pathway ◽  
3D Cell Culture ◽  
Current Therapy ◽  
Beta Catenin ◽  
Cell Culture Model ◽  
Novel Therapy ◽  
3 Dimensional ◽  
Culture Model

Abstract Background : The Wnt/beta-catenin pathway is dysregulated in pancreatic cancer and is reported to be associated with poor prognosis, indicating the need for identification of novel agents to improve the efficacy of current therapy or have better activity. Therefore in the present study we explored the anticancer activity of PNU-74654 alone or in combination with gemcitabine in 2 and 3 dimensional cell culture model of pancreatic cancer. Methods: The MTT assay was applied to determine the viability of PC cancerous cells (PCC), while the cytotoxicity of this agent was evaluated in 3D cell culture model (spheroid). The effects of PNU-74654 was investigated in established cell migration/invasion assays. Result: The expression of candidate genes affecting the cell cycle, migration, and Wnt/b-catenin pathway was evaluated at mRNA and/or proteins by RT-PCR or Western blot. PNU-74654 inhibited the cell growth at IC50 of 122±0.4 umol/L, and had a synergistic effect on the antiproliferative properties of gemcitabine by modulating the Wnt pathway. The PNU-74654/gemcitabine combination reduced the migratory and invasiveness of PC cells, compared to control cells through perturbation of E-cadherin. Conclusion: In aggregate our findings demonstrated the profound antitumor properties of PNU-74654 in pancreatic cancer, supporting further studies to evaluate the therapeutic impact of this novel therapy to target Wnt pathway in the treatment of pancreatic cancer.

scholarly journals Adrenomedullin is Up-regulated in Patients With Pancreatic Cancer and Causes Insulin Resistance in β Cells and Mice

2012 ◽  
Vol 143 (6) ◽  
pp. 1510-1517.e1 ◽  
Author(s):  
Gaurav Aggarwal ◽  
Vijaya Ramachandran ◽  
Naureen Javeed ◽  
Thiruvengadam Arumugam ◽  
Shamit Dutta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pancreatic Cancer ◽  
Β Cells

scholarly journals In vitro model of inflammatory, hypoxia, and cancer stem cell signaling in pancreatic cancer using heterocellular 3-dimensional spheroids

2018 ◽  
Author(s):  
Megha Suresh ◽  
George Mattheolabakis ◽  
Amit Singh ◽  
Mansoor Amiji
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Cell Lines ◽  
Pancreatic Tumor ◽  
Stem Cell Markers ◽  
3 Dimensional

AbstractIntroductionAs one of the most aggressive cancers worldwide, pancreatic cancer is associated with an extremely poor prognosis. The pancreatic tumor microenvironment consists of cancer cells and other tumor associated cells. Cross-talk between these different cell types through various signaling molecules results in the development of a more aggressive and malignant phenotype. Additionally, due to the highly dysregulated vasculature of tumors, the inner tumor core becomes hypoxic and eventually necrotic. Therefore, there is a need for the development of a physiologically relevant in vitro model that recapitulates these dynamic cell-cell interactions and the 3-dimensional (3D) structure of pancreatic tumors.MethodsFour different 3D co-culture spheroid models using different combinations of Panc-1 tumor cells, J774.A1 macrophages, and NIH-3T3 fibroblast cell lines were reproducibly developed using the hanging drop technique in order to mimic the tumor microenvironment and to evaluate the differences in expression of various inflammatory, hypoxia, and cancer stem cell markers, including IL-8, TNF-α, TGF-β, HIF-1α HIF-2α, SCF, and LDH-A. Additionally, immunofluorescence studies were employed to investigate whether these spheroids tested positive for a cancer stem cell population.ResultsPronounced differences in morphology as well as expression of signalling markers were observed using qPCR, indicative of strong influences of co-culturing different cell lines. These models also tested positive for cancer stem cell (CSCs) markers based on immunofluorescence and qPCR analysis.ConclusionOur results demonstrate the potential of 3D co-culture spheroid models to capture the inflammatory and hypoxic markers of pancreatic tumor microenvironment. We further demonstrate the presence of cancer cells with stem cell markers, similar to actual pancreatic cancer tumor. These spheroids present excellent in vitro system to study tumor-immune-stromal cell interactions as well as test deliverability of potential therapeutics in the tumor microenvironment with accurate physical and physiological barriers.

scholarly journals How pancreatic adenocarcinoma might cause diabetes? The role of TGF- β

2021 ◽  
pp. 05-10
Author(s):  
Hanan F. Aly
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Adenocarcinoma ◽  
De Novo ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Β Cells ◽  
Selective Depletion ◽  
New Onset

Pancreatic ductal adenocarcinoma (PDAC) is a deadly sickness that stays incurable due to past due diagnosis, which renders any healing intervention challenging. Most PDAC sufferers expand de novo diabetes, which exacerbates their morbidity and mortality. How PDAC triggers diabetes continues to be unfolding. Using a mouse version of KrasG12D-pushed PDAC, which faithfully recapitulates the development of the human sickness, we determined a large and selective depletion of β-cells, taking place very early on the degrees of preneoplastic lesions. Mechanistically, it turned into observed that accelerated TGF beta (TGF-β) signaling throughout PDAC development induced erosion of β-mobileular mass thru apoptosis. Suppressing TGF-β signaling, both pharmacologically thru TGF-β immunoneutralization or genetically thru deletion of Smad4 or TGF-β kind II receptor (TβRII), afforded size able safety in opposition to PDAC-pushed β-mobileular depletion. From a translational perspective, each activation of TGF-β signaling and depletion of β-cells often arise in human PDAC, imparting a mechanistic cause of the pathogenesis of diabetes in PDAC sufferers, and similarly implicating new- onset diabetes as a capability early prognostic marker for PDAC. In this mini review we try to analyze the principle relationships between pancreatic cancer and diabetes and vice versa in addition to the implication of TGF-β signaling as a likely goal for attenuating diabetes in pancreatic most cancers patients.

3DFT-Flash MR Imaging of Pancreatic Cancer with Gadopentetate Dimeglumine

1996 ◽  
Vol 37 (1P1) ◽  
pp. 190-194 ◽  
Author(s):  
T. Murakami ◽  
K. Tsuda ◽  
H. Nakamura ◽  
K. Osuga ◽  
K. Tomoda ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mr Imaging ◽  
Spin Echo ◽  
Gadopentetate Dimeglumine ◽  
Pancreatic Tumors ◽  
Breath Hold ◽  
Surgical Removal ◽  
Slice Thickness ◽  
Mr Images ◽  
3 Dimensional

Purpose: We evaluated the usefulness of dynamic 3-dimensional Fourier transformation (3DFT) fast low angle shot (FLASH) MR imaging using gadopentetate dimeglumine (Gd-DTPA) to assess the extent of pancreatic cancer. Material and Methods: Breath-hold 3DFT-FLASH MR images (20/4; 25° flip angle; 7 partitions; 3–5-mm slice thickness) were obtained before the administration of 0.1 mmol/kg of Gd-DTPA, just after (early phase), and 1 and 2 min (late phases) after in 14 patients with pancreatic cancer. All patients underwent surgical removal or laparotomy. We compared the findings of T1-, T2-, and postcontrast T1-weighted spin-echo (conventional SE) and 3DFT-FLASH imaging with histologic or surgical findings. Results: Dynamic MR images could delineate the pancreatic tumors more clearly than the conventional SE images, and were useful for diagnosing vessel invasion. The contrast-to-noise ratio between the pancreatic cancer and the surrounding pancreatic parenchyma was significantly higher with the dynamic 3DFT-FLASH image than with the conventional SE images (p<0.01). Conclusion: Dynamic 3DFT-FLASH MR imaging with Gd-DTPA is useful in delineating and evaluating the extent of pancreatic cancer.

Pancreatic cancer cells selectively stimulate islet β cells to secrete amylin

1998 ◽  
Vol 114 (1) ◽  
pp. 130-138 ◽  
Author(s):  
Xianzhong Ding ◽  
Peter R. Flatt ◽  
Johan Permert ◽  
Thomas E. Adrian
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Β Cells ◽  
Pancreatic Cancer Cells

scholarly journals Biphenotypic Differentiation of Pancreatic Cancer in 3-Dimensional Culture

Pancreas ◽  
2019 ◽  
Vol 48 (9) ◽  
pp. 1225-1231 ◽  
Author(s):  
Yoshihisa Matsushita ◽  
Barbara Smith ◽  
Michael Delannoy ◽  
Maria A. Trujillo ◽  
Peter Chianchiano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
3 Dimensional

scholarly journals Dedifferentiation process driven by radiotherapy-induced HMGB1/TLR2/YAP/HIF-1α signaling enhances pancreatic cancer stemness

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Lirong Zhang ◽  
Hui Shi ◽  
Hongbo Chen ◽  
Aihua Gong ◽  
Yanfang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Independent Manner ◽  
X Ray ◽  
Pancreatic Cancer Cells ◽  
Coculture Model ◽  
Dying Cells

Abstract Differentiated cancer cells reacquiring stem cell traits following radiotherapy may enrich cancer stem cells and accelerate tumor recurrence and metastasis. We are interested in the mechanistic role of dying cells-derived HMGB1 in CD133− pancreatic cancer cells dedifferentiation following radiotherapy. We firstly confirmed that X-ray irradiation induced differentiation of CD133− pancreatic cancer cells, from either sorted from patient samples or established cell lines, into cancer stem-like cells (iCSCs). Using an in vitro coculture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133− pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. Inhibiting the expression and activity of HMGB1 attenuated the dedifferentiation stimulating effect of irradiated, dying cells on C133− pancreatic cancer cells in vitro and in PDX models. Mechanistically, HMGB1 binding with TLR2 receptor functions in a paracrine manner to affect CD133− pancreatic cancer cells dedifferentiation via activating Hippo-YAP pathway and HIF-1α expression in oxygen independent manner in vitro and in vivo. We conclude that X-ray irradiation induces CD133− pancreatic cancer cell dedifferentiation into a CSC phenotype, and inhibiting HMGB1 may be a strategy to prevent CSC enrichment and further pancreatic carcinoma relapse.

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