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.

Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling

“…Rhim et al reported that some components of the tumor stroma act to restrain tumor growth, and the reduction of stromal content by sonic hedgehog gene deletion led to the emergence of more aggressive tumors that exhibited undifferentiated histology, increased vascularity, and heightened proliferation (50). In addition, Liot et al also demonstrated that the TME contains anti-tumor components (51). Although it is well known that the Wnt signaling pathway promotes tumor progression (52, 53), Green et al proved that Wnt3a derived from CAFs can both promote and inhibit the growth of breast tumors (54).…”

“…In addition, Liot et al. also demonstrated that the TME contains anti-tumor components ( 51 ). Although it is well known that the Wnt signaling pathway promotes tumor progression ( 52 , 53 ), Green et al.…”

Identification of Genes Associated With Laryngeal Squamous Cell Carcinoma by Weighted Gene Co-Expression Network Analysis

“…There is an urgent need to identify more potential targets for drugs and biomarkers for early diagnosis [20][21][22]. ECM is a fundamental and important component of all tissue organs and has been found to interact with tumor cells and regulate tumor growth, proliferation, differentiation, adhesion and metastasis [23][24][25]. Here, we con rmed that most of the Core-ECM genes like Collagens, Proteoglycans and Glycoproteins were high expressed in LSCC compared with adjacent normal mucosa tissues (Figure S2).…”

Recent Advances in Mass Spectrometry-Based Glycomic and Glycoproteomic Studies of Pancreatic Diseases

“…This dense environment changes cellular properties, and it has been suggested that desmoplasia is a cause of the chemoresistance of pancreatic cancer (Whatcott et al, 2012). The role of the ECM in PDACstromal interactions was recently reviewed (Liot et al, 2021).…”