Application of anti-LRP/LR specific antibodies on neoplastic cell lines for metastatic cancer treatment

Abstract

The 37kDa/67kDa laminin receptor (LRP/LR) is thought to play a major role in the adhesion to laminin and consequently invasion resulting in the metastasis of tumor cells. This receptor is reported to be over-expressed in several neoplastic cell lines and is believed to increase tumor aggressiveness. This research aims at determining whether the application of anti-LRP/LR specific antibody (IgG1-iS18) on neoplastic cell lines would result in a decrease in invasion and adhesion. All neoplastic cell lines had significantly increased cell surface LRP/LR levels compared to NIH/3T3 cells, with the most notable increase seen in SW480 cells (10.98%). Due to a positive correlation between the cell surface LRP/LR levels and invasion potential we propose that an increased LRP/LR level correlates to an increased ability to invade. A significantly decreased adhesion potential was noted in all neoplastic cell lines except the non-invasive MCF-7 cell line, upon application of IgG1-iS18, 21% decrease in HT-1080 cells, 14% in HeLa, 20% in LNCaP, 48% and 74% in A549 and SW480 cells, respectively. Incubation with the anti-LRP/LR antibody IgG1-iS18 resulted in a significant reduction of the invasive potential of HT-1080 (44%), A549 (33%), HeLa (69%), SW480 (91%) and LNCaP cells (38%). Furthermore, a high Pearson’s correlation coefficient between adhesion potential and invasive potential was seen, confirming that adhesion is indeed a pre-requisite for invasion. The significant reduction in invasion and adhesion of HT-1080, A549, HeLa, SW480 and LNCaP cells upon application of the IgG1-iS18 antibody suggests that this macromolecule might act as a promising therapeutic tool for the treatment of various metastatic cancer types.