Abstract
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.
Highlights
Cancer is a global burden that has been shown to be the leading cause of death in economically developed countries and the second leading cause of death in economically developing countries[1]
The green fluorescence in the images below is indicative of cell surface LRP/LR as cells were non-permeabilized and the secondary antibody was shown to not bind non-as confirmed by the controls depicted in Fig.1 b) and Fig.1 c) below
Several studies have revealed that, on the cell surface, various tumorigenic cell lines exhibit an overexpression of the 37 kDa/ 67 kDa LRP/LR, suggesting that the LRP/LR-laminin1 interaction may be pivotal for cancer cells to undergo metastasis[21]
Summary
Cancer is a global burden that has been shown to be the leading cause of death in economically developed countries and the second leading cause of death in economically developing countries[1]. According to the World Cancer Research Fund (WCRF), an estimated 14.1 million cases of cancer were diagnosed in the year 2012 and it is predicted that approximately 24 million new cases of cancer will be diagnosed by the year 2035, globally It has been reported that approximately 782000 cases of liver cancer and 352000 cases of leukaemia were diagnosed in the year 2012 Cells are largely dependent on the extracellular matrix (ECM), which is the non-cellular component of all tissues and organs that provides a physical scaffold to cellular components and assists with initiation of essential biochemical processes needed for proper tissue differentiation, homeostasis and morphogenesis[2]. The non-integrin 37-kDa/67-kDa laminin receptor (LRP/LR) is a major component of the extracellular matrix, assisting in numerous physiological processes[3,4,5]. It is suggested that 37-kDa LRP is the precursor of the 67-kDa high affinity laminin receptor LR, the exact mechanism by which the precursor forms the receptor is unknown[6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
