Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins

Abstract

Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide and is predicted to become second in 2030 in industrialized countries if no therapeutic progress is made. Among the different types of pancreatic cancers, Pancreatic Ductal Adenocarcinoma (PDAC) is by far the most represented one with an occurrence of more than 90%. This specific cancer is a devastating malignancy with an extremely poor prognosis, as shown by the 5-years survival rate of 2-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Pancreatic tumors progress with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. This malignancy is characterized by an extremely dense stroma deposition around lesions, accompanied by tissue hypovascularization and a profound immune suppression. Altogether, these combined features make access to cancer cells almost impossible for conventional chemotherapeutics and new immunotherapeutic agents, thus contributing to the fatal outcomes of the disease. Initially ignored, the Tumor MicroEnvironment (TME) is now the subject of intensive research related to PDAC treatment and could contain new therapeutic targets. In this review, we will summarize the current state of knowledge in the field by focusing on TME composition to understand how this specific compartment could influence tumor progression and resistance to therapies. Attention will be paid to Tenascin-C, a matrix glycoprotein commonly upregulated during cancer that participates to PDAC progression and thus contributes to poor prognosis.

Keywords: extracellular matrix; pancreatic ductal adenocarcinoma; stroma; tenascin; tumor microenvironment.

Figure 1

Schematic representations and optical microscopic images of normal pancreas, pancreatitis, and progression from PanIN1 to invasive PDAC. Particular focus is made on development of desmoplastic stroma. Pancreatitis schematic representation from Yao et al. (2), PanIN progression inspired from Morris et al. (3). ID, Interlobular Duct; IL, Islet of Langerhans; A, Acini; BPC, Benign Pancreatic Cells; WBC, White Blood Cells. Healthy pancreas scheme has been obtained from OpenStax College - Anatomy & Physiology. http://cnx.org/content/col11496/1.6/.