title: Bone morphogenetic protein -4 and -5 in pancreatic cancer--novel bidirectional players.
abstract: Bone morphogenetic proteins (BMPs) are multifunctional signaling molecules that have gained increasing interest in cancer research. To obtain a systematic view on BMP signaling in pancreatic cancer we first determined the mRNA expression levels of seven BMP ligands (BMP2-BMP8) and six BMP specific receptors in pancreatic cancer cell lines and normal pancreatic tissue. BMP receptor expression was seen in all cancer and normal samples. Low expression levels of BMP5 and BMP8 were detected in cancer cells compared to the normal samples, whereas BMP4 expression was elevated in 25% of the cases. The impact of BMP4 and BMP5 signaling on cell phenotype was then evaluated in five pancreatic cancer cell lines. Both ligands suppressed the growth of three cell lines (up to 79% decrease in BMP4-treated PANC-1 cells), mainly due to cell cycle changes. BMP4 and BMP5 concurrently increased cell migration and invasion (maximally a 10.8-fold increase in invaded BMP4-treated PANC-1 cells). The phenotypic changes were typically associated with the activation of the canonical SMAD pathway, although such activation was not observed in the PANC-1 cells. Taken together, BMP4 and BMP5 simultaneously inhibit the growth and promote migration and invasion of the same pancreatic cells and thus exhibit a biphasic role with both detrimental and beneficial functions in pancreatic cancer progression.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Finland. siruvirtanen@gmail.com
authors.forename: Siru
authors.initials: S
authors.lastname: Virtanen
authors.forename: Emma-Leena
authors.initials: EL
authors.lastname: Alarmo
authors.forename: Saana
authors.initials: S
authors.lastname: Sandström
authors.forename: Minna
authors.initials: M
authors.lastname: Ampuja
authors.forename: Anne
authors.initials: A
authors.lastname: Kallioniemi
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D055417:Bone Morphogenetic Protein 5 / Q000378:metabolism*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
chemical_list: C525814:BMP5 protein, human; D055415:Bone Morphogenetic Protein 4; D055417:Bone Morphogenetic Protein 5; D051785:Smad Proteins; D052004:Bone Morphogenetic Protein Receptors