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 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.
Highlights
Cancer, a highly complex disease, has become one of the leading causes of death globally
Research has shown that the interaction between laminin-1 and the 37kDa/67kDa laminin receptor precursor (LRP/LR) is essential for metastasis to occur [24,25]
Early- and Late-Stage Colorectal Cancer Cells Exhibit High Percentages Of laminin receptor precursor/67kDa high-affinity laminin receptor (LRP/LR) and Significantly Greater LRP/LR Levels on the Cell Surface Compared to Poorly Invasive MCF-7 Controls
Summary
A highly complex disease, has become one of the leading causes of death globally. The World Health Organization predicts a 75% increase in total cancer cases worldwide by the year 2030 [1]. South Africa ranks 50th in highest cancer incidences, and a recent study suggests that South Africa could face a 78% increase in the number of cancer cases by 2030 [2]. The present study focuses on colorectal cancer, the third most common cancer type, with over 1.4 million new cases diagnosed in 2012, including 600,000 deaths (http://www.wcrf.org/int/ cancer-facts-figures/worldwide-data). Untreated colorectal cancer is the second most fatal type after lung cancer, yet if diagnosed in its early stages, it can be effectively treated [2]. Colorectal cancer can be classified into four primary stages: early (stage I), middle (stages II and III) and late (stage IV), which results in metastasis
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