Anti-LRP/LR-specific antibody IgG1-iS18 impedes adhesion and invasion of pancreatic cancer and neuroblastoma cells

Abstract

BackgroundCancer has become a global burden due to its high incidence and mortality rates, with an estimated 14.1 million cancer cases reported worldwide in 2012 particularly as a result of metastasis. Metastasis involves two crucial steps: adhesion and invasion, and the non-integrin receptor; the 37-kDa/67-kDa laminin receptor precursor/ high affinity laminin receptor (LRP/LR) has been shown to be overexpressed on the surface of tumorigenic cells, thus being implicated in the enhancement of these two crucial steps. The current study investigated the role of LRP/LR on the aggressiveness of pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells with respect to their adhesive and invasive potential.MethodsAsPC-1 and IMR-32 cells were utilized as the experimental cell lines for the study. Cell surface LRP/LR levels were visualised and quantified on the experimental and control (MCF-7) cell lines via confocal microscopy and flow cytometry, respectively. Total LRP/LR levels in the cell lines were assessed by Western blotting and the adhesive and invasive potential of the above-mentioned cell lines was determined before and after supplementation with the anti-LRP/LR specific antibody IgG1-iS18. Statistical significance of the data was confirmed via the use of the two-tailed student’s t-test and Pearson’s correlation coefficient.ResultsFlow cytometry revealed that AsPC-1 and IMR-32 cells displayed significantly higher cell surface LRP/LR levels in comparison to the MCF-7 control cell line. However, Western blotting and subsequent densitometric analysis revealed that all three tumorigenic cell lines displayed no significant difference in total LRP/LR levels. The treatment of AsPC-1 and IMR-32 cells with IgG1-iS18 caused a significant reduction in the adhesive and invasive potential of the cells to laminin-1 and through the ECM-like Matrigel™, respectively. Pearson’s correlation coefficients indicated a high correlation, thus suggesting a directly proportional relationship between cell surface LRP/LR levels and the adhesive and invasive potential of AsPC-1 and IMR-32 cells.ConclusionThese findings suggest that through the interference of the LRP/LR-laminin-1 interaction, the anti-LRP/LR specific antibody IgG1-iS18 may act as an alternative therapeutic tool for the treatment of metastatic pancreatic cancer and neuroblastoma.

Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors

“…Given their various implications in cellular regulation, it is not surprising to find elevated LAMR expression in various cancers (282)(283)(284)(285)(286)(287)(288) and their involvement in tumor cell growth, migration, invasion, and aggressiveness (266,282,289). Importantly, laminin 1-LAMR interaction was shown to be implicated in tumor cell adhesion (271,290) and invasion (291,292) and LAMR down-regulation was shown to promote tumor cell apoptosis (293)(294)(295)(296). Whether this is mediated by laminin 1-dependent activation of LAMR remains unknown.…”

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.…”