Disease relevance of Il24

• Overexpression of the melanoma differentiation associated gene-7 (mda-7) in vitro results in suppression of lung cancer cell proliferation [1].
• These data suggest that the combination of Ad-mda7 with Herceptin may be a novel therapy for breast cancer patients whose tumors overexpress Her-2/neu [2].
• In vitro, adenovirus-mediated mda-7 gene (Ad-mda7) transfer to murine fibrosarcoma (UV2237m; MCA16) and normal (10T1/2) cells significantly inhibited growth (P=0.001) and induced apoptosis in tumor cells but not in normal cells [3].
• Melanoma differentiation associated gene-7 (Mda-7)/IL-24 was previously cloned into ZD55 (an adenovirus with E1B55 deleted) to form ZD55-IL-24, which had much better antitumor effect than Ad-IL-24 [4].

High impact information on Il24

• These data suggest that the induction of Il24 by oncogenes may support tumor growth at the early stages of cancer [5].
• Following a large genetic screen using RP3-expressing thyroid cells, we identified a highly abundant transcript and later identified it as interleukin 24 (Il24), a cytokine with diverse tumor suppressor and inflammatory activities [5].
• Molecular analysis showed enhanced tumor cell apoptosis and reduced VEGF and CD31 expression in Ad-mda7 plus bevacizumab-treated tumors [6].
• In vitro, treatment of human umbilical vein endothelial cells with conditioned medium from Ad-mda7 plus bevacizumab-treated lung tumor cells showed reduced VEGF ligand-receptor binding, and decreased cell survival, resulting in growth arrest and apoptosis [6].
• The interleukin (IL)-24/melanoma differentiation associated gene-7 (mda-7) is a member of the IL-10 cytokine family [7].

Biological context of Il24

• Compared to individual treatments, the combination of Ad-mda7 and Herceptin elicits supra-additive antitumor activity in Her-2/neu-overexpressing tumor cell lines: increased cell death, cell cycle block and apoptosis [2].
• The melanoma differentiation-associated gene-7 (mda-7) is a member of the interleukin-10 cytokine family and a novel tumor suppressor gene [2].
• Thus Ad-mda7 treatment of syngeneic tumors induces tumor cell death and promotes immune activation, leading to anticancer immunity [3].

Anatomical context of Il24

• In this study, we evaluate the effects of treatment with Ad-mda7 and Herceptin combination therapy in a panel of Her-2/neu-overexpressing cell lines, and in established tumors in nude mice [2].
• Ad-mda7 does not alter cell surface Her-2/neu levels, but the combination of Ad-mda7+Herceptin results in increased expression of cell surface E-cadherin with concomitant translocation of beta-catenin from the nucleus to the cell membrane [2].

Analytical, diagnostic and therapeutic context of Il24

• In vivo, treatment of subcutaneous lung tumor xenografts with bevacizumab plus Ad-mda7 resulted in significant tumor growth inhibition and improved survival compared to tumor growth in control mice [6].

References