Abstract
The identification of new biomarkers and targets for tailored therapy in human colorectal cancer (CRC) onset and progression is an interesting challenge.CRC tissue produces an excess of ox-LDL, suggesting a close correlation between lipid dysfunction and malignant transformation. Lectin-like oxidized LDL receptor-1 (LOX-1) is involved in several mechanisms closely linked to tumorigenesis.Here we report a tumor specific LOX-1 overexpression in human colon cancers: LOX-1 results strongly increased in the 72% of carcinomas (P<0.001), and strongly overexpressed in 90% of highly aggressive and metastatic tumours (P<0.001), as compared to normal mucosa. Moreover LOX-1 results modulated since the early stage of the disease (adenomas vs normal mucosa; P<0.001) suggesting an involvement in tumor insurgence and progression.The in vitro knockdown of LOX-1 in DLD-1 and HCT-8 colon cancer cells by siRNA and anti-LOX-1 antibody triggers to an impaired proliferation rate and affects the maintenance of cell growth and tumorigenicity. The wound-healing assay reveals an evident impairment in closing the scratch. Lastly knockdown of LOX-1 delineates a specific pattern of volatile compounds characterized by the presence of a butyrate derivative, suggesting a potential role of LOX-1 in tumor-specific epigenetic regulation in neoplastic cells.The role of LOX-1 as a novel biomarker and molecular target represents a concrete opportunity to improve current therapeutic strategies for CRC. In addition, the innovative application of a technology focused to the identification of LOX-1 driven volatiles specific to colorectal cancer provides a promising diagnostic tool for CRC screening and for monitoring the response to therapy.
Highlights
Colorectal cancer (CRC) is currently one of the principal causes of deaths in the Western countries [1]
Low grade carcinomas displayed a substantial increase of LDL receptor-1 (LOX-1) expression in the cytoplasm, whereas no positive staining was detected in the nucleus counterstained with haematoxylin
LOX-1 expression resulted strongly increased in the 72% of carcinomas
Summary
Colorectal cancer (CRC) is currently one of the principal causes of deaths in the Western countries [1]. Increased CRC risk is associated with obesity, diabetes, high cholesterol and atherosclerosis, which are components of a disease state known as “metabolic syndrome” [2, 3]. CRC tissue produces and accumulates an excess of ox-LDL, suggesting a close correlation between lipid dysfunction and malignant transformation. This hypothesis is further supported by the observation that inhibition of cholesterol production by statins protects against cancerogenesis [8] and that among patients with newly diagnosed coronary artery disease the prevalence of CRC was greater [9]
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