PMID- 22184093
OWN - NLM
STAT- MEDLINE
DCOM- 20120419
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 92
IP  - 3
DP  - 2012 Mar
TI  - SOX2 contributes to melanoma cell invasion.
PG  - 362-70
LID - 10.1038/labinvest.2011.188 [doi]
AB  - The mechanisms of melanoma invasion are poorly understood despite extensive 
      inquiry. SRY (sex determining region Y)-box 2 (SOX2) is an embryonic stem cell 
      transcription factor that has recently been discovered to be expressed in human 
      melanoma where it is associated with dermal invasion and primary tumor thickness. 
      To assess the potential role of SOX2 expression in melanoma invasion, we examined 
      patient melanomas and humanized melanoma xenografts, and noted preferential SOX2 
      expression in cells that interfaced and infiltrated dermal stroma. Experimental 
      knockdown (KD) of SOX2 mRNA and protein in A2058 melanoma cells with high 
      constitutive SOX2 expression resulted in 4.5-fold decreased invasiveness in vitro 
      compared with controls (P<0.0001). Conversely, when G361 cells that normally 
      express low SOX2 were transduced to overexpress SOX2 mRNA and protein, a 3.8-fold 
      increase in invasiveness was observed (P=0.0004). Among 84 invasion-related 
      genes, RT-PCR screening revealed that SOX2 KD resulted in striking decrease in 
      matrix metalloproteinase-3 (MMP-3), an endopeptidase associated with cleavage of 
      the extracellular matrix. Quantitatively, SOX2 KD diminished MMP-3 mRNA by 87.8%. 
      MMP-3 KD in SOX2-expressing A2058 cells served to inhibit invasion, although to a 
      lesser degree than SOX2 KD. Finally, immunostaining of patient and xenograft 
      melanomas revealed coordinate SOX2 and MMP-3 expression in regions of stromal 
      infiltration. These data implicate SOX2 expression in melanoma invasion, and 
      suggest a role for MMP-3 as one potential mediator of this process.
FAU - Girouard, Sasha D
AU  - Girouard SD
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Laga, Alvaro C
AU  - Laga AC
FAU - Mihm, Martin C
AU  - Mihm MC
FAU - Scolyer, Richard A
AU  - Scolyer RA
FAU - Thompson, John F
AU  - Thompson JF
FAU - Zhan, Qian
AU  - Zhan Q
FAU - Widlund, Hans R
AU  - Widlund HR
FAU - Lee, Chung-Wei
AU  - Lee CW
FAU - Murphy, George F
AU  - Murphy GF
LA  - eng
GR  - P30 AR042689/AR/NIAMS NIH HHS/United States
GR  - P50 CA093683/CA/NCI NIH HHS/United States
GR  - R01 CA138231/CA/NCI NIH HHS/United States
GR  - P50 CA93683/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111219
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor/*metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Melanoma/*metabolism/pathology
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Invasiveness
MH  - Neoplasm Transplantation
MH  - SOXB1 Transcription Factors/*metabolism
PMC - PMC3887365
MID - NIHMS544161
EDAT- 2011/12/21 06:00
MHDA- 2012/04/20 06:00
PMCR- 2014/01/10
CRDT- 2011/12/21 06:00
PHST- 2011/12/21 06:00 [entrez]
PHST- 2011/12/21 06:00 [pubmed]
PHST- 2012/04/20 06:00 [medline]
PHST- 2014/01/10 00:00 [pmc-release]
AID - S0023-6837(22)02697-6 [pii]
AID - 10.1038/labinvest.2011.188 [doi]
PST - ppublish
SO  - Lab Invest. 2012 Mar;92(3):362-70. doi: 10.1038/labinvest.2011.188. Epub 2011 Dec 
      19.