Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI) -anchored membrane protein that is highly conserved in mammalian species. PrPc has the characteristics of adhesive molecules and is thought to play a role in cell adhesion and membrane signaling. Here we investigated the possible role of PrPc in the process of invasiveness and metastasis in gastric cancers. PrPc was found to be highly expressed in metastatic gastric cancers compared to nonmetastatic ones by immunohistochemical staining. PrPc significantly promoted the adhesive, invasive, and in vivo metastatic abilities of gastric cancer cell lines SGC7901 and MKN45. PrPc also increased promoter activity and the expression of MMP11 by activating phosphorylated ErK1/2 in gastric cancer cells. MEK inhibitor PD98059 and MMP11 antibody (Ab) significantly inhibited in vitro invasive and in vivo metastatic abilities induced by PrPc. N-terminal fragment (amino acid 24-90) was suggested to be an indispensable region for signal transduction and invasion-promoting function of PrPc. Taken together, the present work revealed a novel function of PrPc that the existence of N-terminal region of PrPc could promote the invasive and metastatic abilities of gastric cancer cells at least partially through activation of MEK/ERK pathway and consequent transactivation of MMP11.
The purpose of this study was to study changes in choroidal thickness (ChT) and choroidal blood perfusion (ChBP), and the correlation between them, in guinea pig myopia. METHODS. The reliability of optical coherence tomography angiography (OCTA) for measuring ChT and ChBP was verified in guinea pigs, after cervical dislocation (n ¼ 7) or temporal ciliary artery transection (n ¼ 6). Changes in refraction, axial length, ChT, and ChBP were measured during spontaneous myopia (n ¼ 9), monocular form-deprivation myopia (FDM, n ¼ 13), or lens-induced myopia (LIM, n ¼ 14), and after 4 days of recovery from FDM and LIM. RESULTS. The abolition (by cervical dislocation) or reduction (by temporal ciliary artery transection) of ChBP, and of the associated changes in ChT, were verified by OCTA, thus validating the method of measurement. In the spontaneous myopia group, ChT and ChBP were reduced by 25.2% and 31.9%, respectively. In FDM eyes, mean 6 SD ChT and ChBP decreased significantly compared with the untreated fellow eyes (ChT fellow: 76.13 6 9.34 lm versus 64.76 6 11.15 lm for FDM; ChBP fellow: 37.87 6 6.37 3 10 3 versus 30.27 6 6.06 3 10 3 for FDM) and increased after 4 days of recovery (ChT: 77.94 6 12.57 lm; ChBP: 37.41 6 6.11 3 10 3). Effects of LIM were similar to those of FDM. Interocular differences in ChT and ChBP were significantly correlated in each group (FDM: R ¼ 0.71, P < 0.001; LIM: R ¼ 0.53, P < 0.001). CONCLUSIONS. ChT and ChBP were significantly decreased in all three models of guinea pig myopia, and they both increased during recovery. Changes in ChT were positively correlated with changes in ChBP. Therefore, it is possible that the changes of ChT are responsible for the changes of ChBP or vice versa. Keywords: myopia, choroidal thickness, choroidal blood perfusion, guinea pig M yopia is commonly recognized as an ocular disorder that carries significant risks of visually blinding complications. 1,2 In recent decades, the prevalence and severity of myopia have been on the rise, and it is estimated that by 2050 there will be 4.76 billion people with myopia and 0.94 billion with high myopia. 3-6 Meanwhile, the total cost of myopia correction is also increasing, becoming a relatively large economic burden in urbanized countries. 7-9 With the drastic increase in the public health impact, as well as the socioeconomic burden of myopia, many researchers have focused on investigating the mechanisms underlying myopia development. Twenty years ago, in a seminal study, Wallman et al. found that choroidal thickness (ChT) in chicks significantly increased and decreased in response to positive and negative lens-induced defocus, causing hyperopic and myopic refractive shifts, respectively. 10 On removal of the imposed negative lens defocus, the choroid of the now myopic eye thickened, moving the retina forward toward the defocused image plane. Such bidirectional growth regulation has stimulated researchers to study the choroid as a target tissue for myopia control, and ChT has been investigated as a surrogate marker for...
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