title: Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression.
abstract: Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation.
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Carly
authors.initials: C
authors.lastname: Bunston
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hodson
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Jeyna
authors.initials: J
authors.lastname: Resaul
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Ping-Hui
authors.initials: PH
authors.lastname: Sun
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Shuo
authors.initials: S
authors.lastname: Cai
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Lucy K
authors.initials: LK
authors.lastname: Satherley
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Bosanquet
authors.affiliation: Department of Surgery, Morriston Hospital, ABM University Health Board, Swansea, SA6 6NL, UK.
authors.forename: Bilal
authors.initials: B
authors.lastname: Al-Sarireh
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Tian
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Hao
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
mesh_terms: D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D002449:Cell Aggregation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9