Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma

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http://hdl.handle.net/10138/189042

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Riihila , P , Nissinen , L , Farshchian , M , Kallajoki , M , Kivisaari , A , Meri , S , Grenman , R , Peltonen , S , Peltonen , J , Pihlajaniemi , T , Heljasvaara , R & Kahari , V-M 2017 , ' Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma ' , The American Journal of Pathology , vol. 187 , no. 5 , pp. 1186-1197 . https://doi.org/10.1016/j.ajpath.2017.01.006

Julkaisun nimi: Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma
Tekijä: Riihila, Pilvi; Nissinen, Liisa; Farshchian, Mehdi; Kallajoki, Markku; Kivisaari, Atte; Meri, Seppo; Grenman, Reidar; Peltonen, Sirkku; Peltonen, Juha; Pihlajaniemi, Taina; Heljasvaara, Ritva; Kahari, Veli-Matti
Tekijän organisaatio: Medicum
Seppo Meri / Principal Investigator
Department of Bacteriology and Immunology
Päiväys: 2017-05
Kieli: eng
Sivumäärä: 12
Kuuluu julkaisusarjaan: The American Journal of Pathology
ISSN: 0002-9440
DOI-tunniste: https://doi.org/10.1016/j.ajpath.2017.01.006
URI: http://hdl.handle.net/10138/189042
Tiivistelmä: 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 kerati-nocytes (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 rotes of C3 and CFB in the development of cSCC and identify them as biomarkers and potential therapeutic targets in this metastatic skin cancer.
Avainsanat: HUMAN KERATINOCYTES
TUMOR MICROENVIRONMENT
ALTERNATIVE PATHWAY
LUNG-CANCER
FACTOR-I
FACTOR-H
EXPRESSION
PROGRESSION
SKIN
ACTIVATION
3111 Biomedicine
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by_nc_nd
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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