Molecular tools directed against LRP/LR, such as antibodies and small interfering RNA, could prove to be effective in the prevention of metastasis and angiogenesis while inducing apoptosis in cancers. Moreover, these strategies could also be applied to AD where LRP/LR is seen to facilitate the production and internalization of the neurotoxic Aβ peptide. This review provides a comprehensive overview of the mechanisms by which LRP/LR is involved in eliciting pathogenic events, while showing how the use of patented approaches targeting this receptor could be used to treat them.

Adhesion and invasion have been identified as the two key components of metastasis. The 37 kDa/67 kDa laminin receptor (LRP/LR) is thought to enhance these two processes thus endorsing the progression of cancer. Here we report on LRP/LR and the metastatic potential of MDA-MB 231 breast and WHCO1 oesophageal cancer cells. Western blot analysis revealed a significant increase in total laminin receptor precursor (LRP) levels of breast and oesophageal cancer cells in comparison to non-invasive MCF-7 breast cancer cells, whereas LRP/LR cell surface levels in both cell lines were not significantly different to those of MCF-7 cells as analysed by flow cytometry. Incubation of breast and oesophageal cancer cells with the anti-LRP/LR specific antibody, IgG1-iS18, resulted in significant reduction in the adhesive potential of WHCO1 and MDA-MB 231 cells by 92% and 16%, respectively. Moreover, invasion was significantly impeded by 98% and 25% for WHCO1 and MDA-MB 231 cells, respectively. Pearson’s correlation coefficients proved a positive correlation between total LRP/LR levels and invasive potential as well as between the adhesive and invasive potential of breast and oesophageal cancer cells. Our findings suggest that through interference of the LRP/LR-laminin-1 interaction, anti-LRP/LR specific antibody IgG1-iS18 may act as a possible alternative therapeutic tool for metastatic breast and oesophageal cancer treatment.

Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson's correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction.

Cancer is a global burden due to high incidence and mortality rates and is ranked the second most diagnosed disease amongst non-communicable diseases in South Africa. A high expression level of the 37kDa/67kDa laminin receptor (LRP/LR) is one characteristic of cancer cells. This receptor is implicated in the pathogenesis of cancer cells by supporting tumor angiogenesis, metastasis and especially for this study, the evasion of apoptosis. In the current study, the role of LRP/LR on cellular viability of breast MCF-7, MDA-MB 231 and WHCO1 oesophageal cancer cells was investigated. Western blot analysis revealed that total LRP expression levels of MCF-7, MDA-MB 231 and WHCO1 were significantly downregulated by targeting LRP mRNA using siRNA-LAMR1. This knockdown of LRP/LR resulted in a significant decrease of viability in the breast and oesophageal cancer cells as determined by an MTT assay. Transfection of MDA-MB 231 cells with esiRNA-RPSA directed against a different region of the LRP mRNA had similar effects on LRP/LR expression and cell viability compared to siRNA-LAMR1, excluding an off-target effect of siRNA-LAMR1. This reduction in cellular viability is as a consequence of apoptosis induction as indicated by the exposure of the phosphatidylserine protein on the surface of breast MCF-7, MDA-MB 231 and oesophageal WHCO1 cancer cells, respectively, detected by an Annexin-V/FITC assay as well as nuclear morphological changes observed post-staining with Hoechst. These observations indicate that LRP/LR is crucial for the maintenance of cellular viability of breast and oesophageal cancer cells and recommend siRNA technology targeting LRP expression as a possible novel alternative technique for breast and oesophageal cancer treatment.

BackgroundDifferent histo-pathological types and treatment response patterns of Idiopathic nephrotic syndrome (INS) have been associated with differences in ethnicity and geographical location.ObjectiveTo provide an update on the steroid response and renal histo-pathological pattern in children treated for INS.MethodMedical records of children with INS treated at the Charlotte Maxeke Johannesburg Academic Hospital were reviewed.ResultsMean age was 5.3 years ± 2.8. The majority (68.1%) of the 163 children were of the black racial group. The highest rate of INS was seen in the 2–6 year age group (71.2%). The black racial group had the highest rate (42/111; 37.8%) of focal segmental glomerulosclerosis (FSGS), and the white race had the highest rate (9/14; 64.3%) of minimal change disease (MCD). Ninety four (57.7%) patients were steroid sensitive (SSNS) while 69 patients (42.3%) were steroid resistant (SRNS). Minimal change disease was the most common histo-pathological type seen in SSNS (60%), while FSGS was the most common observed in patients who had SRNS (65.2%).ConclusionThere appears to be a higher rate of FSGS in all the racial groups, and also a higher rate of MCD in the black race group, when compared to previous reports.