scholarly journals Tumor–Stroma Cross-Talk in Human Pancreatic Ductal Adenocarcinoma: A Focus on the Effect of the Extracellular Matrix on Tumor Cell Phenotype and Invasive Potential

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 158 ◽  
Author(s):  
Patrizia Procacci ◽  
Claudia Moscheni ◽  
Patrizia Sartori ◽  
Michele Sommariva ◽  
Nicoletta Gagliano
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Ductal Adenocarcinoma ◽  
Cell Phenotype ◽  
Type I ◽  
Invasive Potential ◽  
Emt Markers ◽  
E Cadherin

The extracellular matrix (ECM) in the tumor microenvironment modulates the cancer cell phenotype, especially in pancreatic ductal adenocarcinoma (PDAC), a tumor characterized by an intense desmoplastic reaction. Because the epithelial-to-mesenchymal transition (EMT), a process that provides cancer cells with a metastatic phenotype, plays an important role in PDAC progression, the authors aimed to explore in vitro the interactions between human PDAC cells and ECM components of the PDAC microenvironment, focusing on the expression of EMT markers and matrix metalloproteinases (MMPs) that are able to digest the basement membrane during tumor invasion. EMT markers and the invasive potential of HPAF-II, HPAC, and PL45 cells grown on different ECM substrates (fibronectin, laminin, and collagen) were analyzed. While N-cadherin, αSMA, and type I collagen were not significantly affected by ECM components, the E-cadherin/β-catenin complex was highly expressed in all the experimental conditions, and E-cadherin was upregulated by collagen in PL45 cells. Cell migration was unaffected by fibronectin and delayed by laminin. In contrast, collagen significantly stimulated cell migration and the secretion of MMPs. This study’s results showed that ECM components impacted cell migration and invasive potential differently. Collagen exerted a more evident effect, providing new insights into the understanding of the intricate interplay between ECM molecules and cancer cells, in order to find novel therapeutic targets for PDAC treatment.

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

scholarly journals Activation of transmembrane receptor tyrosine kinase DDR1-STAT3 cascade by extracellular matrix remodeling promotes liver metastatic colonization in uveal melanoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Wei Dai ◽  
Shenglan Liu ◽  
Shubo Wang ◽  
Li Zhao ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cells ◽  
Uveal Melanoma ◽  
Specific Inhibitor ◽  
Type I ◽  
Matrix Remodeling ◽  
Metastatic Colonization ◽  
Tgf Β1

AbstractColonization is believed a rate-limiting step of metastasis cascade. However, its underlying mechanism is not well understood. Uveal melanoma (UM), which is featured with single organ liver metastasis, may provide a simplified model for realizing the complicated colonization process. Because DDR1 was identified to be overexpressed in UM cell lines and specimens, and abundant pathological deposition of extracellular matrix collagen, a type of DDR1 ligand, was noted in the microenvironment of liver in metastatic patients with UM, we postulated the hypothesis that DDR1 and its ligand might ignite the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver. We tested this hypothesis and found that DDR1 promoted these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver. Mechanistically, UM cells secreted TGF-β1 which induced quiescent hepatic stellate cells (qHSCs) into activated HSCs (aHSCs) which secreted collagen type I. Such a remodeling of extracellular matrix, in turn, activated DDR1, strengthening survival through upregulating STAT3-dependent Mcl-1 expression, enhancing stemness via upregulating STAT3-dependent SOX2, and promoting clonogenicity in cancer cells. Targeting DDR1 by using 7rh, a specific inhibitor, repressed proliferation and survival in vitro and in vivo outgrowth. More importantly, targeting cancer cells by pharmacological inactivation of DDR1 or targeting microenvironmental TGF-β1-collagen I loop exhibited a prominent anti-metastasis effect in mice. In conclusion, targeting DDR1 signaling and TGF-β signaling may be a novel approach to diminish hepatic metastasis in UM.

scholarly journals Repression of the Type I Interferon Pathway Underlies MYC- and KRAS-Dependent Evasion of NK and B Cells in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 10 (6) ◽  
pp. 872-887 ◽  
Author(s):  
Nathiya Muthalagu ◽  
Tiziana Monteverde ◽  
Ximena Raffo-Iraolagoitia ◽  
Robert Wiesheu ◽  
Declan Whyte ◽  
...  
Keyword(s):  
B Cells ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Type I Interferon ◽  
Ductal Adenocarcinoma ◽  
Type I ◽  
Interferon Pathway

scholarly journals BRM270 Inhibits the Proliferation of CD44 Positive Pancreatic Ductal Adenocarcinoma Cells via Downregulation of Sonic Hedgehog Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Do Luong Huynh ◽  
Hyebin Koh ◽  
Nisansala Chandimali ◽  
Jiao Jiao Zhang ◽  
Nameun Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Ductal Adenocarcinoma ◽  
Cell Phenotype ◽  
Sonic Hedgehog Signaling ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Adenocarcinoma Cells

Pancreatic cancer has a poor survival rate as compared to other types of cancer. Surface marker CD44 plays important role in epithelial-mesenchymal transition and cancer stem cell phenotype. Therefore, targeting CD44 positive pancreatic cancer cells might enhance therapies effectiveness. Our previous studies indicated the antitumorigenesis effect of BRM270 in osteosarcoma, lung cancer, and glioblastoma; however there is no evidence on BRM270 impacts on pancreatic cancer growth. In this study, we investigated the effect of BRM270 on the isolated CD44 positive pancreatic ductal adenocarcinoma cells (CD44+PDAC). Results showed that CD44 positive cells undergo apoptosis induced by BRM270. Moreover, BRM270 also inhibits stemness and metastasis traits in CD44+PDAC via Sonic hedgehog signaling pathway and SALL4 expression.In vivostudy indicated that tumor growth derived from CD44+PDAC was suppressed as daily uptake by BRM270 5 mg/kg. These data suggest the alternative approach in antipancreatic tumorigenesis via herbal plants extract and selectively targeting CD44+PDAC cells in tumor.

Abstract 179: Presence of primary cilia in cancer cells correlates with prognosis of pancreatic ductal adenocarcinoma

2014 ◽  
Author(s):  
Katsura Emoto ◽  
Yohei Masugi ◽  
Ken Yamazaki ◽  
Kathryn Effendi ◽  
Hanako Tsujikawa ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Primary Cilia ◽  
Ductal Adenocarcinoma

215 SNAIL AND SLUG, MARKERS OF EPITHELIAL MESENCHYMAL TRANSITION, APPEARED TO BE ALTERED BY ALKYL-PHENOLS, BISPHENOL A AND NONYL-PHENOL, IN OVARIAN CANCER CELLS EXPRESSING ESTROGEN RECEPTORS

2015 ◽  
Vol 27 (1) ◽  
pp. 198 ◽  
Author(s):  
Y.-S. Kim ◽  
K.-C. Choi
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Rt Pcr ◽  
Nonyl Phenol ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Emt Markers ◽  
E Cadherin

The ovary is the important organ to produce oocytes. Any disorder will affect embryo production. Ovarian cancer is one of gynecologic cancers in women which can affect ovarian functions. Oestradiol (E2) may be involved in ovarian cell growth and epithelial-mesenchymal transition (EMT) for diverse functions. EMT is an important process in embryo development and tumour migration or progression. Bis-phenol A (BPA) and nonyl-phenol (NP) have an estrogenic property, which can be suspected as endocrine disrupting chemicals (EDC). In this study, it has been examined whether BPA and NP can cause EMT process and migration in BG-1 ovarian cancer cells. To confirm the effect of these EDCs, BG-1 ovarian cancer cells were cultured and treated with DMSO (0.1%), E2 (10–7 M), BPA (10–6 M) and NP (10–6 M) for 0, 6, and 24 h. The mRNAs were extracted to perform reverse-transcription (RT)-PCR and the changes in the mRNA expressions were analysed by ANOVA test. Following treatments with BPA and NP, alterations of EMT markers; that is, vimentin and E-cadherin, were examined at mRNA levels by RT-PCR. The levels of vimentin were up-regulated by E2, BPA, or NP in a time-dependent manner. In addition, transcriptional factors of EMT response, i.e. snail and slug, were enhanced by these treatments more than 2 times. BG-1 cells were exposed to these EDCs for 0, 24, and 48 h. Vimentin and snail proteins were induced by E2, BPA, or NP, while the expression of E-cadherin was decreased by them. To reveal that this EMT response is affected by oestrogen receptor (ER), the cells were treated with these EDCs in the presence of an ER antagonist, ICI 182 780 (10–6 M). Treatment with ICI 182 780 reversed EDC-induced alteration of these EMT markers, E-cadherin, vimentin, and snail. Since EMT response can cause metastasis, a scratch assay was performed to show migration caused by BPA or NP. BPA or E2 enhanced migratory capability of these BG-1 cells. Taken together, these results indicate that BPA and NP, potential EDC, may have an ability to influence ovarian cancer metastasis via regulating snail and slug genes in ER-positive ovarian cancers. In a future study, their effects in inducing EMT and migration will be tested in a xenograft mouse model.This work was supported by a grant from the Next-Generation BioGreen 21 Program (no. PJ009599), Rural Development Administration, Republic of Korea.

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