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.

37 kDa LRP::FLAG enhances telomerase activity and reduces senescent markersin vitro

“…LRP/LR is a non-integrin transmembrane protein located predominantly on the cell surface, and to a lesser extent intracellularly in the cytosol, peri-nuclear as well as nuclear domains [ 14 , 15 ]. The wide-spread localization of LRP/LR as well as its numerous interactions shared with extracellular matrix proteins allows its key role in multiple processes such as: cell growth, adhesion, differentiation, migration, translational processes and maintenance of nuclear structures required for survival regimens [ 14 - 21 ]. The multi-functionality of LRP/LR includes vital roles in diseases such as cancer [ 14 , 16 - 21 ], prion diseases [ 22 , 23 ] and Alzheimer’s disease [ 24 ].…”

LRP::FLAG reduces phosphorylated tau levels in Alzheimer’s Disease

“…LRP/LR is implicated in numerous diseases, including cancer, prion disorders, ageing and AD. LRP/LR is upregulated in multiple metastatic cancers causing increased metastasis, increased angiogenesis and the impediment of apoptosis [22][23][24][25][26][27][28][29][30][31][32][33][34]. Furthermore, LRP/LR is also involved in both cancer and ageing via a functional relationship with telomerase [35][36][37].…”

Knockdown of LRP/LR induces apoptosis in pancreatic cancer and neuroblastoma cells through activation of caspases

“…Numerous studies have implicated LRP/LR as a key contributor to the pathogenesis of certain viral and bacterial infections [14,15] , prion-protein related diseases such as Transmissible Spongiform Encephalopathies [16] , neurodegenerative diseases such as Alzheimer's disease [17,18] , and several cancer types [19][20][21][22] . Blockage of the interaction between Laminin-1 and LRP/LR by use of the anti-LRP/LR specific antibody IgG1-iS18 has been shown to diminish levels of adhesion and invasion of various cell lines in vitro [19][20][21][22][23][24][25] . Therefore, it is evident that LRP/LR is crucial for metastatic processes and is a promising target for metastatic cancer therapeutics.…”