Unit:
Τομέας Βιοχημείας Μοριακής ΒιολογίαςLibrary of the School of Science
Author:
Παπαδημητροπούλου Ανδριάνα
Dissertation committee:
Εμμανουήλ Φραγκούλης Καθηγητής (Επιβλέπων), Διδώ Βασιλακοπούλου Αναπλ. Καθηγήτρια, Ανδρέας Σκορίλας Καθηγητής
Original Title:
Κατασκευή, απομόνωση και παραγωγή ανασυνδυασμένων τμημάτων ανθρώπινων αντισωμάτων έναντι καρκινικών αντιγόνων
Translated title:
Construction, isolation and production of recombinant human antibody fragments against tumor antigens
Summary:
The purpose of this study was to isolate human antibodies against the
extracellular domain of EMMPRIN, the inducer of metalloproteinases (MMPs), in
order to study its mode of action and consequently prevent the induction of
MMPs.
Additionally, an attempt to elucidate the exact part of the extracellular
domain of EMMRPIN responsible for the production of MMPs was made. Also, as
there were conflicting data for the contribution of glycosylation to MMP
induction,the role of glycosylation in this process was also studied.
In the present study, the entire extracellular region ECD-EMMPRIN and its
sub-regions, IgI and IgII,were separately isolated in their glycosylated and
non-glycosylated forms. Then, their action was studied and attempts were made
in order to isolate inhibitory antibodies against EMMPRIN.
The results showed that glycosylation plays a key role in the induction of MMPs
as only the glycosylated forms could induce MMP-2, with the glycosylated
extracellular domain IgII-EMMPRIN
significantly participating to this induction. Also,no functionally blocking Ab
against the MMP-2 inducing activity of EMMPRIN and cancer cell migration was
produced. Instead, the antibody isolated showed high affinity for the
extracellular domain of EMMPRIN and was able to induce the expression of ΜΜP-2.
Keywords:
Emmprin, Metalloproteinases, Antibody, Cancer, Phages
Number of index pages:
11
Number of references:
237
