title: EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.
abstract: Keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC), is the most common metastatic skin cancer. We have examined the role of Eph/ephrin signaling in the progression of cSCC. Analysis of the expression of EPH and EFN families in cSCC cells and normal epidermal keratinocytes revealed overexpression of EPHB2 mRNA in cSCC cells and cSCC tumors in vivo. Tumor cell-specific overexpression of EphB2 was detected in human cSCCs and in chemically induced mouse cSCCs with immunohistochemistry, whereas the expression of EphB2 was low in premalignant lesions and normal skin. Knockdown of EphB2 expression in cSCC cells suppressed growth and vascularization of cSCC xenografts in vivo and inhibited proliferation, migration, and invasion of cSCC cells in culture. EphB2 knockdown downregulated expression of genes associated with biofunctions cell viability, migration of tumor cells, and invasion of tumor cells. Among the genes most downregulated by EphB2 knockdown were MMP1 and MMP13. Moreover, activation of EphB2 signaling by ephrin-B2-Fc enhanced production of invasion proteinases matrix metalloproteinase-13 (MMP13) and MMP1, and invasion of cSCC cells. These findings provide mechanistic evidence for the role of EphB2 in the early progression of cSCC to the invasive stage and identify EphB2 as a putative therapeutic target in this invasive skin cancer.
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Mehdi
authors: M
authors: Farshchian
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Liisa
authors: L
authors: Nissinen
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors: Elina
authors: E
authors: Siljamäki
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Pilvi
authors: P
authors: Riihilä
authors: Department of Cell Biology and Anatomy, University of Turku, Turku, Finland.
authors: Mervi
authors: M
authors: Toriseva
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Atte
authors: A
authors: Kivisaari
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Risto
authors: R
authors: Ala-Aho
authors: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Markku
authors: M
authors: Kallajoki
authors: Department of Plastic and General Surgery, University of Turku and Turku University Hospital, Turku, Finland.
authors: Esko
authors: E
authors: Veräjänkorva
authors: Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors: Hanne-Kaisa
authors: HK
authors: Honkanen
authors: Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors: Ritva
authors: R
authors: Heljasvaara
authors: Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors: Taina
authors: T
authors: Pihlajaniemi
authors: Department of Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Turku, Finland.
authors: Reidar
authors: R
authors: Grénman
authors: Department of Cell Biology and Anatomy, University of Turku, Turku, Finland.
authors: Juha
authors: J
authors: Peltonen
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Sirkku
authors: S
authors: Peltonen
authors: Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland. Electronic address: veli-matti.kahari@utu.fi.
authors: Veli-Matti
authors: VM
authors: Kähäri
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D036388:Ephrin-B2 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics*; D011897:Random Allocation; D036183:Receptor, EphB2 / Q000235:genetics*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D036388:Ephrin-B2; D012333:RNA, Messenger; C586310:EPHB2 protein, human; D036183:Receptor, EphB2