title: Altered integrin expression patterns shown by microarray in human cutaneous melanoma.
abstract: A large variety of molecular pathways in melanoma progression suggests that no individual molecular alteration is crucial in itself. Our aim was to define the molecular alterations underlying metastasis formation. Gene expression profiling was performed using microarray and qRT-PCR to define alterations between matched primary and metastatic melanoma cell lines. These data were integrated with publicly available unmatched tissue data. The invasiveness of cell lines was determined by Matrigel invasion assays and invasive clones from primary melanoma-derived cell lines were also selected. Two metastatic cell line models were created: the regional lymph node WM983A-WM983A-WM983B and the distant lung WM793B-WM793B-1205Lu metastatic models. The majority of metastasis genes were downregulated and enriched in adhesion and ITGA6-B4 pathways. Upregulation of immune pathways was characteristic of distant metastases, whereas increased Rap1 signaling was specific for regional (sub)cutaneous metastases. qRT-PCR analysis of selected integrins (A2, A3, A4, A9, B5, B8, A6, B1, and B3) highlighted the possible importance of ITGA3/4 and B8 in the metastatic process, distinguishing regional and distant metastases. We identified functionally relevant gene clusters that influenced metastasis formation. Our data provide further evidence that integrin expression patterns may be important in distant metastasis formation.
authors.affiliation: aDepartment of Preventive Medicine, Faculty of Public Health bMTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: Laura
authors.initials: L
authors.lastname: Vizkeleti
authors.forename: Timea
authors.initials: T
authors.lastname: Kiss
authors.forename: Viktoria
authors.initials: V
authors.lastname: Koroknai
authors.forename: Szilvia
authors.initials: S
authors.lastname: Ecsedi
authors.forename: Orsolya
authors.initials: O
authors.lastname: Papp
authors.forename: Istvan
authors.initials: I
authors.lastname: Szasz
authors.forename: Roza
authors.initials: R
authors.lastname: Adany
authors.forename: Margit
authors.initials: M
authors.lastname: Balazs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D049109:Cell Proliferation; D002648:Child; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D016023:Integrins / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics* / Q000556:secondary; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D016023:Integrins