PMID- 30825266
OWN - NLM
STAT- MEDLINE
DCOM- 20200724
LR  - 20210109
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 23
IP  - 5
DP  - 2019 May
TI  - Complement C3a promotes proliferation, migration and stemness in cutaneous 
      squamous cell carcinoma.
PG  - 3097-3107
LID - 10.1111/jcmm.13959 [doi]
AB  - BACKGROUND: Complement C3 has been shown to be highly expressed in cutaneous 
      squamous cell carcinoma (cSCC) tumour tissues and is correlated with tumour cell 
      growth. This study aimed to investigate the mechanism of C3 in cSCC malignant 
      transformation. METHODS: C3 expression was analysed in cSCC cell lines A431, 
      Tca8113, SCC13, HSC-5 and HSC-1 and in immortalized HaCaT keratinocytes. 
      Proliferation and migration of cSCC were determined after C3a exposure. 
      Expression of cyclin D1, cyclin E, vascular endothelial growth factor (VEGF), 
      pro-matrix metalloproteinase 1 (pro-MMP1), pro-matrix metalloproteinase 2 
      (pro-MMP2), stemness factors, GSK-3beta, and beta-catenin were analyzed. Tumour growth 
      was examined in a murine xenograft model. RESULTS: C3 expression was much more 
      highly expressed in all cSCC cell lines than in HaCaT cells. C3a treatment 
      significantly promoted cSCC cell proliferation and migration and upregulated 
      cyclin D1, cyclin E, VEGF, pro-MMP1 and pro-MMP2 expression, which were impeded 
      by the C3aR antagonist. Moreover, the expression of stemness factors Sox-2, 
      Nanog, Oct-4, c-Myc and CD-44 was stimulated by C3a and slowed by C3aR 
      disruption. Knockdown of Sox-2 by siRNA transfection suppressed cell 
      proliferation and migration, constrained VEGF secretion and inhibited pro-MMP1 
      and pro-MMP2 expression. C3a also activated the Wnt and beta-catenin pathway in cSCC 
      cells. Disruption of C3aR expression dampened tumour growth and the expression of 
      Wnt-1, beta-catenin and Sox-2 in the xenograft model. CONCLUSIONS: C3a enhanced cell 
      proliferation, migration and stemness in cSCC, and this activity was correlated 
      with activation of the Wnt and beta-catenin pathway.
CI  - (c) 2019 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Fan, Zhuo
AU  - Fan Z
AD  - Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, China.
AD  - Department of Dermatology, The First Affiliated Hospital of Xi'an Medical 
      University, Xi'an, China.
FAU - Qin, Jingjing
AU  - Qin J
AD  - Department of Dermatology, The First Affiliated Hospital of Xi'an Medical 
      University, Xi'an, China.
FAU - Wang, Dandan
AU  - Wang D
AD  - Department of Dermatology, The First Affiliated Hospital of Xi'an Medical 
      University, Xi'an, China.
FAU - Geng, Songmei
AU  - Geng S
AUID- ORCID: 0000-0003-3046-1513
AD  - Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, China.
LA  - eng
PT  - Journal Article
DEP - 20190301
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Wnt1 Protein)
RN  - 0 (beta Catenin)
RN  - 80295-42-7 (Complement C3a)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/*genetics
MH  - Complement C3a/*genetics
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Heterografts
MH  - Humans
MH  - Mice
MH  - Neoplasm Proteins/genetics
MH  - Neoplastic Stem Cells/metabolism/pathology
MH  - Signal Transduction
MH  - Skin Neoplasms/*genetics/pathology
MH  - Wnt1 Protein/genetics
MH  - beta Catenin/genetics
PMC - PMC6484302
OTO - NOTNLM
OT  - complement C3a
OT  - cutaneous squamous cell carcinoma
OT  - migration
OT  - proliferation
OT  - stemness
COIS- The authors declare no conflict of interest.
EDAT- 2019/03/03 06:00
MHDA- 2020/07/25 06:00
PMCR- 2019/05/01
CRDT- 2019/03/03 06:00
PHST- 2018/07/23 00:00 [received]
PHST- 2018/09/17 00:00 [accepted]
PHST- 2019/03/03 06:00 [pubmed]
PHST- 2020/07/25 06:00 [medline]
PHST- 2019/03/03 06:00 [entrez]
PHST- 2019/05/01 00:00 [pmc-release]
AID - JCMM13959 [pii]
AID - 10.1111/jcmm.13959 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2019 May;23(5):3097-3107. doi: 10.1111/jcmm.13959. Epub 2019 Mar 
      1.