title: Contribution of in vitro comparison of colorectal carcinoma cells from primary and metastatic lesions to elucidation of mechanisms of tumor progression and response to anticancer therapy.
abstract: Colorectal cancer has been a leading cause of cancer-related morbidity and mortality. For the research and individualization of therapy, primary cell lines of the colorectal cancer appear to be still an invaluable tool. We evaluated the differences in metastatic potential between four isolated primary colon cancer cells and cells derived from their lymph node metastasis. These results were compared with correspond immortalized cells-SW480 and SW620, respectively. The ability to migrate was tested using real-time measurement in xCELLigence system. Expressions of molecules involved in adhesion and invasion processes were examined using RT-PCR and western blot analysis. Furthermore, impact of cytotoxic effect of selected chemotherapeutics (irinotecan, oxaliplatin) and biological therapy (bevacizumab, cetuximab, panitumumab) was assessed by the WST assay. As expected, cell lines derived from lymph node migrated more aggressively and higher expression of adhesion molecules ICAM-1, EpCAM, and N-cadherin was detected. The expression of MMP-2 and -9 was elevated, on the other hand, in cell lines derived from primary tumor cancer cells as well as the expression of miR-21, miR-29a, and miR-200a. The most pronounced cytotoxic effect has been recorded with oxaliplatin and irinotecan (IC50 = 48.23 resp. 0.11 μg/ml), especially in cells originating from lymph node metastases. In total, comparison of isolated cell lines and immortalized cell lines has shown many similarities, as well as several differences. Adhesion/invasion molecules and several miRNAs, which play an important role in tumor development and the invasive and migratory behavior, could be a useful therapeutic target in malignant colorectal cancer.
authors.affiliation: The Fingerland Department of Pathology, Faculty of Medicine and Faculty Hospital in Hradec Králové, Charles University in Prague, Sokolská 581, Hradec Kralove, CZ-500 05, Czech Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Krbal
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové, CZ-500 38, Czech Republic. hanusovav@lfhk.cuni.cz.
authors.forename: Veronika
authors.initials: V
authors.lastname: Hanušová
authors.affiliation: The Fingerland Department of Pathology, Faculty of Medicine and Faculty Hospital in Hradec Králové, Charles University in Prague, Sokolská 581, Hradec Kralove, CZ-500 05, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Soukup
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové, CZ-500 38, Czech Republic.|Department of Oncology and Radiotherapy, Faculty of Medicine and Faculty Hospital in Hradec Králové, Charles University in Prague, Sokolská 581, Hradec Kralove, CZ-500 05, Czech Republic.
authors.forename: Stanislav
authors.initials: S
authors.lastname: John
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, CZ-500 05, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Matoušková
authors.affiliation: The Fingerland Department of Pathology, Faculty of Medicine and Faculty Hospital in Hradec Králové, Charles University in Prague, Sokolská 581, Hradec Kralove, CZ-500 05, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Ryška
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D035683:MicroRNAs; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Anticancer therapy; Colorectal carcinoma; Lymph node metastasis; Tumor progression; microRNA