title: Collagens XV and XVIII show different expression and localisation in cutaneous squamous cell carcinoma: type XV appears in tumor stroma, while XVIII becomes upregulated in tumor cells and lost from microvessels.
abstract: As the second most common skin malignancy, cutaneous squamous cell carcinoma (cSCC) is an increasing health concern, while its pathogenesis at molecular level remains largely unknown. We studied the expression and localisation of two homologous basement membrane (BM) collagens, types XV and XVIII, at different stages of cSCC. These collagens are involved in angiogenesis and tumorigenesis, but their role in cancer development is incompletely understood. Quantitative RT-PCR analysis revealed upregulation of collagen XVIII, but not collagen XV, in primary cSCC cells in comparison with normal human epidermal keratinocytes. In addition, the Ha-ras-transformed invasive cell line II-4 expressed high levels of collagen XVIII mRNA, indicating upregulation in the course of malignant transformation. Immunohistochemical analyses of a large human tissue microarray material showed that collagen XVIII is expressed by tumor cells from grade 1 onwards, while keratinocytes in normal skin and in premalignant lesions showed negative staining for it. Collagen XV appeared instead as deposits in the tumor stroma. Our findings in human cSCCs and in mouse cSCCs from the DMBA-TPA skin carcinogenesis model showed that collagen XVIII, but not collagen XV or the BM markers collagen IV or laminin, was selectively reduced in the tumor vasculature, and this decrease associated significantly with cancer progression. Our results demonstrate that collagens XV and XVIII are expressed in different sites of cSCC and may contribute in a distinct manner to processes related to cSCC tumorigenesis, identifying these collagens as potential biomarkers in the disease.
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland.|Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Sanna-Maria
authors.initials: SM
authors.lastname: Karppinen
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland.|Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Hanne-Kaisa
authors.initials: HK
authors.lastname: Honkanen
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland.|Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Ritva
authors.initials: R
authors.lastname: Heljasvaara
authors.affiliation: MediCity Research Laboratory and Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Pilvi
authors.initials: P
authors.lastname: Riihilä
authors.affiliation: Department of Pathology, University of Oulu/Oulu University Hospital, Oulu, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Autio-Harmainen
authors.affiliation: Department of Pathology, University of Oulu/Oulu University Hospital, Oulu, Finland.|Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland.|Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Harjunen
authors.affiliation: Department of Pathology, University of Oulu/Oulu University Hospital, Oulu, Finland.
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Väisänen
authors.affiliation: Department of Pathology, University of Oulu/Oulu University Hospital, Oulu, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Väisänen
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland.|Department of Dermatology, University of Oulu/Oulu University Hospital, Oulu, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Hurskainen
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland.|Department of Dermatology, University of Oulu/Oulu University Hospital, Oulu, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Tasanen
authors.affiliation: MediCity Research Laboratory and Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kähäri
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland.|Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Pihlajaniemi
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism*; D043170:Collagen Type XVIII / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D051379:Mice; D012878:Skin Neoplasms / Q000378:metabolism*
chemical_list: C085811:COL15A1 protein, human; D043170:Collagen Type XVIII; C553732:collagen XV, mouse; D003094:Collagen
keywords: collagen XV; collagen XVIII; cutaneous squamous cell carcinoma; skin carcinogenesis; tumor stroma