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Loss of MDA-7 expression with progression of melanoma
Julie A Ellerhorst1, Victor G Prieto, Suhendan Ekmekcioglu
1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4095, USA. jaellerh@mail.mdanderson.org
Purpose:
Ectopic transfer of the melanoma differentiation-associated gene-7 (mda-7) has been shown in vitro to suppress growth and induce apoptosis in a variety of human tumor cell lines; similar effects are not elicited in normal cells. Thus, the mda-7 gene seems to function as a novel tumor suppressor, and there is interest in the potential of mda-7 gene transfer as cancer therapy. The objective of this study was to determine if MDA-7 protein is lost during primary melanoma progression from superficial to invasive stages and from localized to metastatic tumor. As a secondary objective, we analyzed MDA-7 protein expression in primary melanomas for correlation with predictors of outcome and with survival.
Materials And Methods:
MDA-7 protein expression was evaluated by immunohistochemistry in 41 primary melanomas and 41 metastases, including 24 paired samples. Each sample was scored for the percentage of positive cells and the overall intensity of immunolabeling.
Results:
Significant decreases in MDA-7 immunostaining, reflected in both number and intensity scores, were observed when comparing the intraepidermal and superficially invasive portions with the deeply invasive portions of primary tumors. Significant differences were also observed when comparing primary tumors to paired metastases.
Conclusion:
Downregulation of MDA-7 expression in primary melanomas facilitates progression to invasive and metastatic stages. These data support the development of Ad-mda7 as gene therapy for advanced melanoma.
Insights
Melanoma differentiation-associated gene-7 (MDA-7) protein decreases as melanoma progresses. This loss of MDA-7 expression correlates with invasive and metastatic melanoma, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Melanoma differentiation-associated gene-7 (mda-7) exhibits tumor suppressor activity in vitro.
- mda-7 gene transfer is being explored as a potential cancer therapy.
- Understanding mda-7 expression during melanoma progression is crucial.
Purpose of the Study:
- To determine if MDA-7 protein is lost during melanoma progression from superficial to invasive stages.
- To assess MDA-7 protein loss from localized to metastatic tumors.
- To correlate MDA-7 expression with melanoma outcome predictors and survival.
Main Methods:
- Immunohistochemistry was used to evaluate MDA-7 protein expression.
- 41 primary melanomas and 41 metastases, including 24 paired samples, were analyzed.
- Samples were scored for the percentage of positive cells and immunolabeling intensity.
Main Results:
- A significant decrease in MDA-7 immunostaining was observed from superficial to deeply invasive portions of primary tumors.
- MDA-7 expression was significantly lower in primary tumors compared to paired metastases.
- Both the number of positive cells and the intensity of staining decreased with tumor progression.
Conclusions:
- Downregulation of MDA-7 expression facilitates melanoma progression to invasive and metastatic stages.
- These findings support the development of Ad-mda7 for advanced melanoma gene therapy.
- MDA-7 downregulation is a key event in melanoma advancement.