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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.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Rumer KK,Post MD,Larivee RS,Zink M,Uyenishi J,Kramer A,Teoh D,Bogart K,Winn VD

doi

10.1530/ERC-11-0379

subject

Has Abstract

pub_date

2012-11-19 00:00:00

pages

827-40

issue

eissn

1351-0088

issn

1479-6821

pii

ERC-11-0379

journal_volume

pub_type

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Siglec-6 is expressed in gestational trophoblastic disease and affects proliferation, apoptosis and invasion.