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.

Murdocca, M., Mango, R., Pucci, S., Biocca, S., Testa, B., Capuano, R., et al. (2016). The lectin-like oxidized LDL receptor-1: A new potential molecular target in colorectal cancer. ONCOTARGET, 7(12), 14765-14780 [10.18632/oncotarget.7430].

The lectin-like oxidized LDL receptor-1: A new potential molecular target in colorectal cancer

Murdocca, M;MANGO, RUGGIERO;PUCCI, SABINA;BIOCCA, SILVIA;Capuano, R;PAOLESSE, ROBERTO;ORLANDI, AUGUSTO;DI NATALE, CORRADO;NOVELLI, GIUSEPPE;SANGIUOLO, FEDERICA CARLA
2016-01-01

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.
2016
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/08 - ANATOMIA PATOLOGICA
English
Con Impact Factor ISI
LOX-1; VOCs analysis; colon cancer; shRNAs
Murdocca, M., Mango, R., Pucci, S., Biocca, S., Testa, B., Capuano, R., et al. (2016). The lectin-like oxidized LDL receptor-1: A new potential molecular target in colorectal cancer. ONCOTARGET, 7(12), 14765-14780 [10.18632/oncotarget.7430].
Murdocca, M; Mango, R; Pucci, S; Biocca, S; Testa, B; Capuano, R; Paolesse, R; Sanchez, M; Orlandi, A; DI NATALE, C; Novelli, G; Sangiuolo, Fc
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/159870
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