University of Oulu

Pilvi Riihilä, Liisa Nissinen, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grénman, Sirkku Peltonen, Juha Peltonen, Taina Pihlajaniemi, Ritva Heljasvaara, Veli-Matti Kähäri, Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma, The American Journal of Pathology, Volume 187, Issue 5, 2017, Pages 1186-1197, ISSN 0002-9440, http://dx.doi.org/10.1016/j.ajpath.2017.01.006. (http://www.sciencedirect.com/science/article/pii/S0002944017302146)

Complement component C3 and complement factor B promote growth of cutaneous squamous cell carcinoma

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Author: Riihilä, Pilvi1,2; Nissinen, Liisa3,2; Farshchian, Mehdi1,2;
Organizations: 1Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland
2MediCity Research Laboratory, University of Turku, Turku, Finland
3Centre of Excellence in Cell-Extracellular Matrix Research and Biocenter Department of Dermatology, University of Turku and Turku University Hospital, Turku, Finland
4Department of Pathology, Turku University Hospital, Turku, Finland
5Haartman Institute, University of Helsinki, Helsinki, Finland
6Department of Otorhinolaryngology–Head and Neck Surgery, Turku University Hospital, Turku, Finland
7Department of Cell Biology and Anatomy, University of Turku, Turku, Finland
8Oulu Center for Cell-Matrix Research, Biocenter Oulu and the Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201708188152
Language: English
Published: Elsevier, 2017
Publish Date: 2017-08-18
Description:

Abstract

Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of complement component C3 and complement factor B (CFB) in the growth of cSCC. Analysis of cSCC cell lines (n = 8) and normal human epidermal keratinocytes (n = 11) with real-time quantitative PCR and Western blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell-specific labeling for C3 and CFB in invasive cSCCs (n = 71) and recessive dystrophic epidermolysis bullosa-associated cSCCs (n = 11) than in cSCC in situ (n = 69), actinic keratoses (n = 63), and normal skin (n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to benign papillomas. Knockdown of C3 and CFB expression inhibited migration and proliferation of cSCC cells and resulted in potent inhibition of extracellular signal-regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhibited growth of human cSCC xenograft tumors in vivo. These results provide evidence for the roles of C3 and CFB in the development of cSCC and identify them as biomarkers and potential therapeutic targets in this metastatic skin cancer.

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Series: American journal of pathology
ISSN: 0002-9440
ISSN-E: 1525-2191
ISSN-L: 0002-9440
Volume: 187
Issue: 5
Pages: 1186 - 1197
DOI: 10.1016/j.ajpath.2017.01.006
OADOI: https://oadoi.org/10.1016/j.ajpath.2017.01.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: Supported by Finnish Cancer Research Foundation grant, Sigrid Juselius Foundation grant, Jane and Aatos Erkko Foundation grant, Turku University Hospital grant (project 13336), the Health Science Council of the Academy of Finland grant 251314 (Center of Excellence 2012-2017), and Finnish Dermatological Association grant (P.R.), Finnish Dermatopathology Society grant (P.R.), Turku University Foundation grant (P.R.), Southwestern Cancer Society of Finland grant (P.R.), The Finnish Medical Foundation and Finnish Cultural Foundation grant (P.R.), Southwestern Finland Regional Fund grant (P.R.)
Copyright information: Copyright 2017 © American Society for Investigative Pathology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0)
  https://creativecommons.org/licenses/by-nc-nd/4.0/