Abstract
BackgroundVery low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cellular signaling. Our group previously reported that enhanced activity of type II VLDLR (VLDLR II), one subtype of VLDLR, promotes adenocarcinoma SGC7901 cells proliferation and migration. The aim of this study is to explore the expression levels of VLDLR II in human gastric, breast and lung cancer tissues, and to investigate its relationship with clinical characteristics and β-catenin expression status.MethodsVLDLR II expression was examined using immunohistochemistry (IHC) and Western blot in tumor tissues from 213 gastric, breast and lung cancer patients, tumor adjacent noncancerous tissues by same methods. Correlations between VLDLR II and clinical features, as well as β-catenin expression status were evaluated by statistical analysis.ResultsThe immunohistochemical staining of VLDLR II showed statistical difference between tumor tissues and tumor adjacent noncancerous tissues in gastric, breast and lung cancers (P = 0.034, 0.018 and 0.043, respectively). Moreover, using Western, we found higher VLDLR II expression levels were associated with lymph node and distant metastasis in gastric and breast cancer (P < 0.05). Furthermore, highly significant positive correlations were found between VLDLR II and β-catenin in gastric cancer (r = 0.689; P < 0.001)breast cancer (r = 0.594; P < 0.001).ConclusionsAccording to the results of the current study, high VLDLR II expression is correlated with lymph node and distant metastasis in gastric and breast cancer patients, the data suggest that VLDLR II may be a clinical marker in cancers, and has a potential link with β-catenin signaling pathway. This is the first to reveal the closer relationship of VLDLR II with clinical information.
Highlights
Very low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cellular signaling
Detection of cellular VLDLR II expression by IHC staining of cancer tissues Using IHC, we examined the distribution of VLDLR II protein in parraffin-embedded mammary tissue sections screened from gastric, breast and lung cancer patients (22, 18, and 24, respectively)
Comparison between tumor and normal tissue revealed that VLDLR II expression levels were significantly increased in gastric, breast and lung cancer patients (P = 0.034, 0.018, and 0.043, respectively; Figure 2)
Summary
Very low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cellular signaling. The very low density lipoprotein receptor (VLDLR) which belongs to the low density lipoprotein receptor (LDLR) family was initially cloned on the basis of its homology to the LDLR [1]. This receptor exhibits domain structures similar to those of the LDLR, except it has an extra repeat of the cysteine-rich ligand-binding domain. A signaling function for the VLDLR has been recognized, as demonstrated by the ability of reelin to modulate neuronal migration, neurodevelopment, and other physiological processes in the central nervous system. The VLDLR appears to regulate biological processes by binding or internalization of ligands, or by transducing extracellular signals across the cell membrane
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