Abstract
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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinomas, characterized by a dismal prognosis due to the high incidence of recurrence and metastases dissemination
Cell Morphology is not Influenced by extracellular matrix (ECM) Components
A similar pattern was observed for results β-catenin immunoreactivity, at the membrane in all experimental conditions. These immunoreactivity, detectable at the plasma membrane in all experimental conditions. These results indicated that the E-cadherin/β-catenin complex was not modified by the considered ECM
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinomas, characterized by a dismal prognosis due to the high incidence of recurrence and metastases dissemination. During PDAC progression, the pancreatic tumor microenvironment (TME) containing extracellular matrix (ECM) components, growth factors, and soluble mediators, and different. Cells 2018, 7, 158 non-parenchymal stromal cells including fibroblasts, inflammatory, and pancreatic stellate cells, undergoes evident qualitative and quantitative modifications. It plays a key role as a modulator of cancer cell phenotype, behavior, and chemoresistance [4,5]. Desmoplasia allows for a complex and dynamic interplay among invading tumor cells, normal host epithelial cells, fibroblasts, ECM components, and released cytokines, growth, and angiogenic factors [8]. ECM represents an important mediator of cancer cell behavior, influencing tumor cell proliferation and migration [9], as well as tissue homeostasis
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