Hani Surianti, DDS, Yin-Hua Shih, MD, Kuo-Wei Chang, PhD, Michael
Yuanchien Chen, DDS, MS, Cheng-Chia Yu, PhD, Dan-Jae Lin, PhD, Shih-Min Hsia, PhD,Heng-Li Huang, PhD, Tzong-Ming Shieh, PhD.
Lysyl oxidase (LOX) is a copper-dependent
enzyme that cross-links collagen and elastin in extracellular matrix.
LOX can be produced in response to hypoxia-induced factors, leading to increased invasion and promotion of metastasis to distant sites.
Increased soluble copper in oral fluids of
long-term betel nut chewers may relate to pathogenesis and metastasis of oral
squamous cell carcinomas (OSCC) through
Investigate copper-enhanced LOX activity in
endothelial cells and LOX overexpression in OSCC cell lines regarding induction of
Chemical treatment and gene transfection
were used to induce LOX overexpression or inhibition in cell lines SAS and SVEC4-10.
LOX mRNA, protein, and activity were
confirmed before tube formation assay and tumorigenesis.
The microvessels were detected by
immunostaining CD31- and LOX protein positive.
ß -aminopropionitrile (ß-APN) inhibited LOX activity and decreased SVEC4-10 tube formation
SILENT
LOX small interfering RNA (LOX siRNA)
OVEREXPRESSION
pLPS-3’EGFP-LOX
SVEC4-10 cells
Scramble siRNA pLPS-3’EGFP (enhanced green fluorescent protein)
LOX overexpression and copper induction
increased LOX activity and SVEC4-10 tube formation.
LOX silencing and ß-aminopropionitrile (ß-
APN) inhibition of LOX activity had opposite effects.
VECTOR ALONE VA LOX OVEREXPRESSION LOXWT2 SAS cells LOXWT1
exogenous
LOX overexpression OSCC cells showed higher and equivalent numbers of LOX activity in both clones.
Proliferating cell nuclear antigen (PCNA)
High LOX expression induced
VA LOXWT2 LOXWT1
High LOX expression clones increased tumor
size in a tumorigenesis model.
The microvascular numbers were higher in
LOX overexpression tumors than in control tumors.
High LOX activity or expression can increase
cell proliferation and angiogenesis leading to
tumor development in vitro and in vivo.
LOX could potentially provide a target for
future anti-cancer or anti-angiogenesis therapies.
