Related Experiment Video
Updated: Jun 25, 2025
07:07
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
12.4K
Modeling Melanoma Heterogeneity In Vitro: Redox, Resistance and Pigmentation Profiles
Larissa Anastacio da Costa Carvalho1,2, Isabella Harumi Yonehara Noma2, Adriana Hiromi Uehara2
1Department of Tumor Biology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Antioxidants (Basel, Switzerland)
|May 25, 2024
Summary
Melanoma subpopulations exhibit distinct traits influencing BRAF inhibitor resistance. Decreased pigmentation and antioxidant defenses, like PRDX1, are linked to therapy resistance in resistant clones.
Area of Science:
- Oncology
- Cancer Biology
- Melanoma Research
Background:
- Tumor microenvironments drive transcriptional plasticity, leading to subpopulations.
- BRAF inhibitors (BRAFis) can select for resistant melanoma clones.
Purpose of the Study:
- To investigate the distinct characteristics of melanoma subpopulations.
- To explore the mechanisms of BRAF inhibitor resistance.
Main Methods:
- Stochastic isolation of three distinct melanoma subpopulations (C1, C2, C3).
- Analysis of morphology, phenotype, function, and gene expression.
- Assessment of sensitivity to BRAF inhibitors and oxidative stress.
Main Results:
- Clones C1 and C3 showed reduced proliferation, increased invasion, and BRAFi resistance.
- Lower expression of MITF, PGC-1α, and PRDX1 was observed in resistant clones (C1, C3).
- Decreased pigmentation markers correlated with therapy resistance and reduced antioxidant defense.
Conclusions:
- Melanoma clonal heterogeneity contributes to BRAF inhibitor resistance.
- PRDX1 expression is linked to clonal heterogeneity and resistance.
- Reduced pigmentation and antioxidant capacity are indicators of therapy resistance.
