Glycomic Analysis of Membrane Glycoproteins with Bisecting Glycosylation from Ovarian Cancer Tissues Reveals Novel Structures and Functions

Biomarkers capable of detecting and
targeting epithelial ovarian
cancer cells for diagnostics and therapeutics would be extremely valuable.
Ovarian cancer is the deadliest reproductive malignancy among women
in the U.S., killing over 14 000 women each year. Both the
lack of presenting symptoms and high mortality rates illustrate the
need for earlier diagnosis and improved treatment of this disease.
The glycosyltransferase enzyme GnT-III encoded by the Mgat3 gene is responsible for the addition of GlcNAc (N-acetylglucosamine) to form bisecting N-linked glycan structures.
GnT-III mRNA expression is amplified in ovarian cancer tissues compared
with normal ovarian tissue. We use a lectin capture strategy coupled
to nano-ESI–RPLC–MS/MS to isolate and identify the membrane
glycoproteins and unique glycan structures associated with GnT-III
amplification in human ovarian cancer tissues. Our data illustrate
that the majority of membrane glycoproteins with bisecting glycosylation
are common to both serous and endometrioid histological subtypes of
ovarian cancer, and several have been reported to participate in signaling
pathways such as Notch, Wnt, and TGFβ.