title: Siglec-6 is expressed in gestational trophoblastic disease and affects proliferation, apoptosis and invasion.
abstract: Sialic acid immunoglobulin-like lectin (Siglec)-6 is a transmembrane receptor that binds leptin. Leptin is an obesity-associated peptide hormone overexpressed in gestational trophoblastic disease (GTD). GTD encompasses several placental abnormalities that range from benign to malignant. Among GTD, molar placentas are characterized by excess proliferation, whereas gestational trophoblastic neoplasias (GTN) have characteristically aggressive invasion. We hypothesized that in GTD, Siglec-6 expression would increase with disease severity and that Siglec-6 and leptin would promote proliferation, inhibit apoptosis and/or promote invasion. Siglec-6 expression patterns were evaluated with particular attention to the diagnostic utility of Siglec-6 in GTD (controls: normal placentas (n=32), hydropic abortus placentas (n=7), non-GTD reproductive tract cancers (n=2); GTD: partial moles (PM; n=11), complete moles (n=24), GTN (n=6)). In normal placentas, Siglec-6 expression dramatically decreased after 8 weeks gestation. Complete molar placentas had significantly higher Siglec-6 expression than controls, but expression was not significantly different from PM. In GTN, Siglec-6 expression was low. These data suggest that Siglec-6 may have diagnostic utility for distinguishing complete moles from normal and hydropic abortus placentas. Functional studies in choriocarcinoma-derived BeWO cells demonstrated a complex interplay between Siglec-6 expression and leptin exposure. In cells lacking Siglec-6, leptin treatment promoted invasion, likely through interaction with LepR leptin receptor, without affecting proliferation or apoptosis. Siglec-6 expression promoted proliferation in a leptin-dependent manner, but protected cells from apoptosis and promoted invasion in a leptin-independent manner. We propose that Siglec-6 and leptin play a role in the aberrant properties characteristic of GTD, namely excess proliferation and invasion.
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado School of Medicine, MS8613, P15-3009, 12700 East 19th Avenue, Aurora, Colorado 80045, USA.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Rumer
authors.forename: Miriam D
authors.initials: MD
authors.lastname: Post
authors.forename: Rhea S
authors.initials: RS
authors.lastname: Larivee
authors.forename: Martina
authors.initials: M
authors.lastname: Zink
authors.forename: Jill
authors.initials: J
authors.lastname: Uyenishi
authors.forename: Anita
authors.initials: A
authors.lastname: Kramer
authors.forename: Deanna
authors.initials: D
authors.lastname: Teoh
authors.forename: Kevin
authors.initials: K
authors.lastname: Bogart
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Winn
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D009361:Neoplasm Invasiveness; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014625:Vaginal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; D020738:Leptin; C120775:SIGLEC6 protein, human