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
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Publish Date: | 2017-08-18 |
Description: |
AbstractCutaneous 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. see all
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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.) |
Academy of Finland Grant Number: |
251314 |
Detailed Information: |
251314 (Academy of Finland Funding decision) |
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/ |