title: The lectin-like oxidized LDL receptor-1: a new potential molecular target in colorectal cancer.
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.
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Murdocca
authors.affiliation: Department of Emergency and Critical Care, Section of Cardiology, Policlinic of Tor Vergata, Rome, Italy.
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Mango
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Pucci
authors.affiliation: Department of Systems Medicine, Tor Vergata University, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Biocca
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Testa
authors.affiliation: Department of Electronic Engineering, Tor Vergata University, Rome, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Capuano
authors.affiliation: Department of Chemical Science and Technology, Tor Vergata University, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Paolesse
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Department of Electronic Engineering, Tor Vergata University, Rome, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: di Natale
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sangiuolo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E
keywords: LOX-1; VOCs analysis; colon cancer; shRNAs