title: A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth.
abstract: SPARC is a matricellular protein that is involved in both pancreatic cancer and diabetes. It belongs to a wider family of proteins that share structural and functional similarities. Relatively little is known about this extended family, but evidence of regulatory interactions suggests the importance of a holistic approach to their study. We show that Hevin, SPOCKs, and SMOCs are strongly expressed within islets, ducts, and blood vessels, suggesting important roles for these proteins in the normal pancreas, while FSTL-1 expression is localised to the stromal compartment reminiscent of SPARC. In direct contrast to SPARC, however, FSTL-1 expression is reduced in pancreatic cancer. Consistent with this, FSTL-1 inhibited pancreatic cancer cell proliferation. The complexity of SPARC family proteins is further revealed by the detection of multiple cell-type specific isoforms that arise due to a combination of post-translational modification and alternative splicing. Identification of splice variants lacking a signal peptide suggests the existence of novel intracellular isoforms. This study underlines the importance of addressing the complexity of the SPARC family and provides a new framework to explain their controversial and contradictory effects. We also demonstrate for the first time that FSTL-1 suppresses pancreatic cancer cell growth.
authors.affiliation: Department of Biomolecular Sciences, Kingston University, Kingston-upon-Thames, UK.
authors.forename: Katrina
authors.initials: K
authors.lastname: Viloria
authors.affiliation: Department of Biomolecular Sciences, Kingston University, Kingston-upon-Thames, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Munasinghe
authors.affiliation: Department of Biomolecular Sciences, Kingston University, Kingston-upon-Thames, UK.
authors.forename: Sharan
authors.initials: S
authors.lastname: Asher
authors.affiliation: Department of Biomolecular Sciences, Kingston University, Kingston-upon-Thames, UK.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bogyere
authors.affiliation: Department of Biomolecular Sciences, Kingston University, Kingston-upon-Thames, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Jones
authors.affiliation: Department of Biomolecular Sciences, Kingston University, Kingston-upon-Thames, UK.
authors.forename: Natasha J
authors.initials: NJ
authors.lastname: Hill
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002135:Calcium-Binding Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D038702:Follistatin-Related Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D038702:Follistatin-Related Proteins; D011509:Proteoglycans; C503126:SPARCL1 protein, human; C504369:SPOCK1 protein, human; C448799:FSTL1 protein, human