Abstract
The non-integrin laminin receptor, here designated the 37-kDa/67-kDa laminin receptor (LRP/LR), is involved in many physiologically relevant processes, as well as numerous pathological conditions. The overexpression of LRP/LR on various cancerous cell lines plays critical roles in tumour metastasis and angiogenesis. This study investigated whether LRP/LR is implicated in the maintenance of cellular viability in lung and cervical cancer cell lines. Here we show a significant reduction in cellular viability in the aforementioned cell lines as a result of the siRNA-mediated downregulation of LRP. This reduction in cellular viability is due to increased apoptotic processes, reflected by the loss of nuclear integrity and the significant increase in the activity of caspase-3. These results indicate that LRP/LR is involved in the maintenance of cellular viability in tumorigenic lung and cervix uteri cells through the blockage of apoptosis. Knockdown of LRP/LR by siRNA might represent an alternative therapeutic strategy for the treatment of lung and cervical cancer.
Highlights
Laminins belong to a large family of extracellular matrix proteins that are involved in a number of biologically significant processes, including cell differentiation, migration, adhesion, growth and signalling [1]
Since the overexpression of LRP has been observed in numerous cancerous cell lines, the cell surface levels of LRP/LR and total levels of LRP on A549 and HeLa cells was determined by flow cytometric analysis and western blotting respectively (Figure 1)
Flow cytometry revealed that 83% and 80% of A549 and HeLa cells, respectively, expressed LRP/LR on their cell surface (Figure 1A and 1B), these values are high in comparison to the LRP/LR cell surface level (57%) of the non-tumorigenic cell line, NIH 3T3, and confirms the results obtained in previous studies [30]
Summary
Laminins belong to a large family of extracellular matrix proteins that are involved in a number of biologically significant processes, including cell differentiation, migration, adhesion, growth and signalling [1]. LRP/LR is a non-integrin cell surface receptor exhibiting a high affinity to laminin-1 [6], and has been found to localize in the cytoplasm [7,8,9], on the cell surface [10,11], in the perinuclear compartment [7,12,13] and in the nucleus [12,13] In each of these locations, LRP/LR is involved in numerous physiological processes including protein synthesis [8], the maturation of the 40S ribosomal subunit [8], acting as a receptor for extracellular matrix components e.g. carbohydrates and elastin [14], interactions with cellular prion protein [13,15] and associations with the histones [12]
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