title: S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is the 5th most common cause of cancer death in the UK and the 4th in the US. The vast majority of deaths following pancreatic cancer are due to metastatic spread, hence understanding the metastatic process is vital for identification of critically needed novel therapeutic targets. An enriched set of 33 genes differentially expressed in common between primary PDAC and liver metastases, when compared to normal tissues, was obtained through global gene expression profiling. This metastasis-associated gene set comprises transcripts from both cancer (S100P, S100A6, AGR2, etc.) and adjacent stroma (collagens type I, III, and V, etc.), thus reinforcing the concept of a continuous crosstalk between the two compartments in both primary tumours and their metastases. The expression of S100P, SFN, VCAN and collagens was further validated in additional primary PDACs and matched liver metastatic lesions, while the functional significance of one of the most highly expressed genes, S100P, was studied in more detail. We show that this protein increases the transendothelial migration of PDAC cancer cells in vitro, which was also confirmed in vivo experiments using a zebrafish embryo model. Thus S100P facilitates cancer cell intravasation/extravasation, critical steps in the hematogenous dissemination of pancreatic cancer cells.
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: Sayka
authors.initials: S
authors.lastname: Barry
authors.forename: Claude
authors.initials: C
authors.lastname: Chelala
authors.forename: Kate
authors.initials: K
authors.lastname: Lines
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamura
authors.forename: Amu
authors.initials: A
authors.lastname: Wang
authors.forename: Federica M
authors.initials: FM
authors.lastname: Marelli-Berg
authors.forename: Caroline
authors.initials: C
authors.lastname: Brennan
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Lemoine
authors.forename: Tatjana
authors.initials: T
authors.lastname: Crnogorac-Jurcevic
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D057705:Transendothelial and Transepithelial Migration; D015027:Zebrafish
chemical_list: D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; C103003:S100P protein, human