Knockdown of proteolipid protein 2 or focal adhesion kinase with an artificial microRNA reduces growth and metastasis of B16BL6 melanoma cells
- Authors:
- Hiroki Ozawa
- Yoshiko Sonoda
- Takaharu Suzuki
- Naomi Yoshida-Hoshina
- Megumi Funakoshi-Tago
- Tadashi Kasahara
View Affiliations
Affiliations: Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan
- Published online on: September 16, 2011 https://doi.org/10.3892/ol.2011.422
-
Pages:
19-24
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Abstract
Proteolipid protein 2 (PLP2) promotes the metastasis of B16F10 cells in an experimental metastasis model. However, the effect of PLP2 on spontaneous metastasis has yet to be demonstrated, and whether PLP2 may become a new therapeutic target for malignant tumors is as yet unknown. In this study, PLP2 or focal adhesion kinase (FAK) microRNA‑based short hairpin RNAs (miRNAs) were used as target molecules to specifically reduce the expression of PLP2 or FAK in B16BL6 cells. In vitro, the knockdown of PLP2 or FAK significantly inhibited cell proliferation, adhesion, migration and invasion. In a spontaneous metastatic tumor model using a footpad injection, the knockdown of PLP2 or FAK markedly inhibited the proliferation of the primary tumor and prevented tumor cells from invading the popliteal lymph nodes. The results indicate that downregulation of PLP2 or FAK may improve outcomes of malignant tumor therapy.
View References
1
|
Fidler IJ: The pathogenesis of cancer
metastasis the ‘seed and soil’ hypothesis revisited. Nat Rev
Cancer. 3:453–458. 2003.
|
2
|
MacDonald IC, Groom AC and Chambers AF:
Cancer spread and micrometastasis development: quantitative
approaches for in vivo models. Bioessays. 24:885–893. 2002.
View Article : Google Scholar : PubMed/NCBI
|
3
|
Hendrix MJ, Seftor EA, Seftor RE,
Kasemeier-Kulesa J, Kulesa PM and Postovit LM: Reprogramming
metastatic tumour cells with embryonic microenvironments. Nat Rev
Cancer. 7:246–255. 2007. View
Article : Google Scholar : PubMed/NCBI
|
4
|
Hanks SK, Ryzhova L, Shin NY and Brábek J:
Focal adhesion kinase signaling activities and their implications
in the control of cell survival and motility. Front Biosci.
8:982–996. 2003. View
Article : Google Scholar : PubMed/NCBI
|
5
|
Kaneda T, Sonoda Y, Ando K, Suzuki T,
Sasaki Y, Oshio T, Tago M and Kasahara T: Mutation of Y925F in
focal adhesion kinase (FAK) suppresses melanoma cell proliferation
and metastasis. Cancer Lett. 270:354–61. 2008. View Article : Google Scholar : PubMed/NCBI
|
6
|
Sonoda Y, Warita M, Suzuki T, Ozawa H,
Fukuda Y, Funakoshi-Tago M and Kasahara T: Proteolipid protein 2 is
associated with melanoma metastasis. Oncol Rep. 23:371–6.
2010.PubMed/NCBI
|
7
|
Raz A, Bucana C, McLellan W and Fidler IJ:
Distribution of membrane anionic sites on B16 melanoma variants
with differing lung colonising potential. Nature. 284:363–364.
1980. View
Article : Google Scholar : PubMed/NCBI
|
8
|
Li S, Dong W, Zong Y, Yin W, Jin G, Hu Q,
Huang X, Jiang W and Hua ZC: Polyethylenimine-colexed plasmid
particles targeting focal adhesion kinase function as melanoma
tumor therapeutics. Mol Ther. 15:515–23. 2007. View Article : Google Scholar : PubMed/NCBI
|
9
|
Sonoda Y, Watanabe S, Matsumoto Y,
Aizu-Yokota E and Kasahara T: FAK is the upstream signal protein of
the phosphatidylinositol 3-kinase-Akt survival pathway in hydrogen
peroxide-induced apoptosis of a human glioblastoma cell line. J
Biol Chem. 274:10566–70. 1999. View Article : Google Scholar : PubMed/NCBI
|
10
|
Qian F, Li YP, Sheng X, Zhang ZC, Song R,
Dong W, Cao SX, Hua ZC and Xu Q: PRL-3 siRNA inhibits the
metastasis of B16-BL6 mouse melanoma cells in vitro and
in vivo. Mol Med. 13:151–9. 2007.PubMed/NCBI
|