Study of the cell surface glycosylation of ovarian carcinoma cells

PhD Seminars

Title: Study of the cell surface glycosylation of ovarian carcinoma cells

Speaker: Eda Machado
 

Laboratory: Glycobiology, ITQB
 

Abstract

Ovarian carcinoma is the leading cause of death from gynecological cancers in many Western countries. Aberrant glycosylation is an important aspect in malignant transformation, normally associated with increased expression of membrane glycoproteins, appearance of novel or truncated oligosaccharides and abnormal types of terminal oligosaccharides containing antigenic determinants like the Lewis (Le) determinants.
The expression of α3/4-fucosyltransferases (FUTs) levels and their products, the Le determinants were studied in ovarian carcinoma cell lines SKOV3, OVM, m130 and GG. It was found that Lex, Ley, sialyl-Lea and Leb were expressed on GG cells. The m130 cell line expressed mostly Lex and Ley, whereas SKOV3 and OVM cells expressed low amounts of intracellular Lex and almost undetectable amounts of Lea. Results also indicated that FUT3 was responsible for the synthesis of Lea, sLea and Leb, while Lex and Ley were synthesized by FUT4 and/or FUT9 in m130 and GG cells. Additionally, overexpression of FUT4, FUT5, FUT6, FUT7 and FUT9 in SKOV3 cells originated de novo synthesis of Lex and/or sLex epitopes, and the overexpression of FUT3 produced the sLea epitope. These newly constructed cell lines may be used to explore the biological roles played by the Le determinants, and thair impact in tumor growth and metastasis.
The N-linked oligosaccharides from total glycoproteins of the SKOV3 cell line were further characterized by high performance anion exchange chromatography with pulsed amperometric detection and matrix assisted laser desorption/ionization time-of-flight mass spectrometry. The results showed that SKOV3 cells were rich in unprocessed oligomannose structures, with low peripheral sialic acid levels. Furthermore, the N-glycosylation of a recombinant secretory glycoprotein, erythropoietin, stably produced from this cell line was characterized. Processed complex-type oligosaccharides with high sialic acid levels were found.
This work will contribute to the knowledge of the glycosylation characteristics of human ovarian cancer cell lines.

Short CV

February 2006 to present: PhD student at the Laboratory of Glycobiology, under the supervision of Dr. Júlia Costa.
August 2004 to January 2006: Fellowship for Initiation to Science at Laboratory of Glycobiology.

December 2003 – Degree in Ciências Químicas e do Ambiente – Biotecnologia, ISEIT, Instituto Piaget - Almada.