Anti-LRP/LR specific antibody IgG1-iS18 significantly impedes adhesion and invasion in early and late stage colorectal carcinoma cells.
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 known as 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 (SW-480 & HT-29) and late (DLD-1) stage colorectal cancer cells has been investigated. Western blotting revealed that early and late stage colorectal cancer cells contained significantly higher total LRP/LR levels compared to poorly invasive MCF-7 breast cancer control cells. Flow cytometry revealed that all three stages of colorectal cancer displayed significantly higher cell surface LRP/LR levels. Furthermore, upon treatment of the colorectal cancer cells with the anti-LRP/LR specific antibody IgG1-iS18, adhesion to laminin-1 was significantly reduced in all three stages. Each stage's invasive potential was determined using the Matrigel™ invasion assay, which revealed that invasion is significantly impeded in all three colorectal cancer stages when the cells are 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 all three stages of colorectal cancer. Hence, these findings indicate the potential for the use of the IgG1-iS18 antibody as a promising therapeutic tool for colorectal cancer patients of early and late stage.
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, The Republic of South Africa (RSA).
Leila
L
Vania
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, The Republic of South Africa (RSA).
Carryn J
CJ
Chetty
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, The Republic of South Africa (RSA).
Eloise
E
Ferreira
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, The Republic of South Africa (RSA).
Stefan F T
SFT
Weiss
37kDa/67kDa laminin receptor; Cancer; LRP/LR; metastasis; therapeutics