Artikel
The role of side-population of malignant melanoma in recurrence, metastasis and prognosis
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Veröffentlicht: | 26. April 2013 |
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Gliederung
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Introduction: Melanoma is the most threatening skin cancer in human. The key point, which influences the prognosis most, is recurrence and metastasis of melanoma. Cancer stem cells (CSCs) are a sub-population of cancer cells, which are related to chemo-resistance, local cancer recur and distant metastasis. Multi-pathway-targeting anti-CSC therapy shed new light on melanoma patient-tailored treatment.
Material and methods: Murine melanoma cell line B16BL6 was investigated as chemo-sensitive and –resistant cell line. Standard chemo-therapy drug Doxirubicin (Dox) was added in cell culture medium. After 1-4 months chemo-drug treatment, side-population cells of B16BL6 were sorted by the Hoechst staining followed with FACS analysis. E-cadherin and β-catenin expression was assessed by immunocytochemistry.
Results: The morphology of B16BL6 was changed from “flagstone" appearance to fibroblast-like style as treated by Dox, and the chemo-resistant cells are full of melanin in cytoplasm. Side-population cells can be enriched in chemo-resistant cells, which increased from 0.96% to 4.7% within 1 month. Meanwhile, the Dox IC50 elevated from 148.91ng/ml to 377.62ng/ml. E-cadherin expressed mainly at cell-membrane area, and cytoplasm-nuclear translocation of β-catenin can be seen as chemo-sensitive to –resistant cells.
Conclusion: Chemo-resistance induced cancer stem-like cell – side-population cells which express EMT-related genes and pathways. We hypothesize that these cells are a source of treatment resistance in vivo and blocking their emergence may prevent treatment failure.