Inhibitory Effect of Melanoma Differentiation Associated Gene-7/Interleukin-24 on Invasion In Vitro of Human Melanoma Cancer Cells

다국어 초록 (Multilingual Abstract)

The acquisition of metastasis potential is a critical point for malignant tumors. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a potential tumor suppress gene and frequently down-regulated in malignant tumors. It has been implicated that overexpression of MDA-7 led to proliferation inhibition in many types of human tumor. Invasion is an important process which is potential to promote tumor metastasis.

However, the role and potential molecular mechanism of mda-7/IL-24 to inhibit the invasion of human melanoma cancer is not fully clear. In this report, we identified a solid role for mda-7/IL-24 in invasion inhibition of human melanoma cancer LiBr cells, including decreasing of adhesion and invasion in vitro, blocking cell cycle, down-regulating the expression of ICAM-1, MMP-2/9, CDK1, the phosphorylation of ERK and Akt, NF-κB and AP-1 transcription activity. Meanwhile, there was an increased expression of PTEN in mda-7/IL-24 over-expression LiBr cells. Our results demonstrated that mda-7/IL-24 is a potential invasion suppress gene, which inhibits the invasion of LiBr cells by the down-regulation of ICAM-1, MMP-2/9, PTEN, and CDK1 expression. The molecular pathways involved were the MAPK/ERK, PI3K-Akt, NF-κB, and AP-1. These findings suggest that mda-7/IL-24 may be used as a possible therapeutic strategy for human melanoma cancer.

참고문헌 (Reference)

1 Adya R, "Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis" 78 : 356-365, 2008

2 Lydka M, "Tumor necrosis factor α-mediated restructuring of the Sertoli cell barrier in vitro involves matrix metalloprotease 9 (MMP9), membrane-bound intercellular adhesion molecule- 1 (ICAM-1) and the actin cytoskeleton" 2 : 294-303, 2012

3 Smith FO, "Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines" 14 : 5610-5618, 2008

4 Turrisi R, "The style project: feasibility of collaborating with salons for prevention and early detection of skin cancer" 148 : 1206-1207, 2012

5 Bonavida B, "The novel role of Yin Yang 1 in the regulation of epithelial to mesenchymal transition in cancer via the dysregulated NF- κB/Snail/YY1/RKIP/PTEN Circuitry" 16 : 211-226, 2011

6 Dent P, "The development of MDA-7/IL-24 as a cancer therapeutic" 128 : 375-384, 2010

7 Herszenyi L, "The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer" 13 : 13240-13263, 2012

8 Gaud G, "TFPI-2 silencing increases tumour progression and promotes metalloproteinase 1 and 3 induction through tumour-stromal cell interactions" 15 : 196-208, 2011

9 Allan C, "Surgery and the management of cutaneous melanoma" 100 : 313-315, 2013

10 Jiang H, "Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda- 7, modulated during human melanoma differentiation, growth and progression" 11 : 2477-2486, 1995

11 Zhang P, "Sequential binding of αVβ3 and ICAM-1 determines fibrin-mediated melanoma capture and stable adhesion to CD11b/CD18 on neutrophils" 186 : 242-254, 2011

12 Sun X, "Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver" 14 : 1122-1131, 2012

13 Lutzky J, "New therapeutic options in the medical management of advanced melanoma" 29 : 249-257, 2010

14 Marchesi F, "Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasis" 21 : 77-82, 2010

15 Fisher PB, "Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): novel gene therapeutic for metastatic melanoma" 224 : 300-307, 2007

16 Chen JS, "Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: association with MMP-9" 39 : 177-186, 2009

17 Hamed HA, "Inhibition of multiple protective signaling pathways and Ad.5/3 delivery enhances mda-7/IL-24 therapy of malignant glioma" 18 : 1130-1142, 2010

18 Chapman PB, "Improved survival with vemurafenib in melanoma with BRAF V600E mutation" 364 : 2507-2516, 2011

19 Hodi FS, "Improved survival with ipilimumab in patients with metastatic melanoma" 363 : 711-723, 2010

20 Parfiniewicz B, "Impact of celecoxib on soluble intercellular adhesion molecule-1 and soluble e-cadherin concentrations in human colon cancer cell line cultures exposed to phytic acid and TNF-alpha" 69 : 1283-1290, 2012

21 Hamai A, "ICAM-1 has a critical role in the regulation of metastatic melanoma tumor susceptibility to CTL lysis by interfering with PI3K/AKT pathway" 68 : 9854-9864, 2008

22 Emdad L, "Historical perspective and recent insights into our understanding of the molecular and biochemical basis of the antitumor properties of mda-7/IL-24" 8 : 391-400, 2009

23 Soerjomataram I, "Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions" 380 : 1840-1850, 2012

24 Eulitt PJ, "Enhancing mda-7/IL-24 therapy in renal carcinoma cells by inhibiting multiple protective signaling pathways using sorafenib and by Ad.5/3 gene delivery" 10 : 1290-1305, 2010

25 Sun B, "Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow" 14 : 292-298, 2005

26 Wang CJ, "Ad.mda-7 (IL-24) selectively induces apoptosis in hepatocellular carcinoma cell lines, suppresses metastasis, and enhances the effect of doxorubicin on xenograft tumors" 18 : 561-574, 2010

27 Eager R, "Ad-MDA-7; INGN 241: a review of preclinical and clinical experience" 8 : 1633-1643, 2008