Anti-LRP/LR–specific antibody IGG1-IS18 significantly impedes adhesion and invasion in early- and late-stage colorectal carcinoma cells

Abstract

Cancer is a highly complex disease that has become one of the leading causes of death globally. Metastasis, a major cause of cancer deaths, requires two crucial events, adhesion and invasion. The 37kDa/67kDa laminin receptor (laminin receptor precursor/high-affinity laminin receptor [LRP/LR]) enhances these two steps, consequently aiding in cancer progression. In this study, the role of LRP/LR in adhesion and invasion of early-stage (SW-480 and HT-29) and late-stage (DLD-1) colorectal cancer cells was investigated. Western blotting revealed that early- and late-stage colorectal cancer cells contained significantly higher total LRP/LR levels compared with poorly invasive MCF-7 breast cancer control cells. Flow cytometry revealed that both stages of colorectal cancer displayed significantly higher cell surface LRP/LR levels. Furthermore, upon treatment of colorectal cancer cells with the anti-LRP/LR–specific antibody IgG1-iS18, adhesion to laminin-1 was significantly reduced in both stages. Each stage’s invasive potential was determined using the Matrigel™ invasion assay, showing that invasion was significantly impeded in both colorectal cancer stages when the cells were incubated with IgG1-iS18. In addition, Pearson’s correlation coefficients propose that both total and cell surface LRP/LR levels are directly proportional to the adhesive and invasive potential of both stages of colorectal cancer. Hence, these findings indicate potential for use of the IgG1-iS18 antibody as a promising therapeutic tool for colorectal cancer patients at both stages.