213
pancreatic cancer cell expressing GPI-anchored PrP to BxPC-3 in wound-healing
assays, BxPC-3 cells migrate much faster. More importantly, when pro-PrP was
converted into GPI-anchored PrP in PIG F and PGA1 expressing BxPC-3 cells,
these cells showed a significant reduction in mobility [ 47 ]. To further confirm that
interactions between FLNa and pro-PrP contribute to cancer cell migration, we
compared the mobility of two melanoma cell lines, M2 and A7. M2 is the sole mela-
noma cell line that does not express FLNa, whereas A7 is an FLNa-expressing cell
line derived from M2. A7 showed a much greater mobility compared to M2.
However, when PrP was downregulated in A7 cells, those A7 cells with reduced PrP
expression migrate significantly slower, thus proving that pro-PrP increases cancer
cell migration via interacting with FLNa [ 30 ]. Moreover, when pro-PrP and FLNa
binding was attenuated in A7 cells by a peptide corresponding to the sequence of
PrP-interacting FLNa domain, A7 cell migration was also greatly inhibited [ 30 ].
This result not only points out the interaction between pro-PrP and FLNa indeed
existed in vivo but also indicates a potential intervention method to interrupt mela-
noma metastasis. Overall, due to posttranslational differences, PrP bestows cell
adhesion and migration through different pathways in interaction with distinct
partner.
0
5
10
15
20
25
30
35
Wound closure%
DMSOZM306416ki8751sar131675DMSOZM306416ki8751sar131675WT DM
Fig. 13.2 CHO cells expressing unglycosylated PrP showed VEGFR2-dependent cell migration
under serum-free culture condition. WT, WT human PrP expressed in CHO cells; DM, unglycosyl-
ated PrP expressed in CHO cells. DMSO, vehicle control; ZM306416, VEGFR1-specific inhibitor;
ki8751, VEGFR2-specific inhibitor; sar131675, VEGFR3-specific inhibitor. Cell wound was
inflicted, and closure was measured 18 h later. Wound closure was quantified based on image J
software)
13 Prion Protein Exacerbates Tumorigenesis