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Updated: Dec 27, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Particulate mediators of the bystander effect linked to suicide and interferon-β transgene expression in melanoma
Lucrecia Agnetti1, Chiara Fondello1, María Florencia Arbe1
1Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Buenos Aires, Argentina.
Abstract:
In the context of comparative oncology, melanoma cells derived from companion animal tumors are good models for optimizing and predicting their in vivo response to therapeutic strategies. Here, we report that human, canine, and feline melanoma cells driven to death by bleomycin, interferon-β gene, or herpes simplex virus thymidine kinase/ganciclovir suicide gene (SG) treatment significantly increased their internal granularity. This fact correlated with the release of a heterogeneous collection of nano- and micro-sized granules as revealed by transmission electron microscopy. While killing lipofected cells, the expressed transgenes and their derived products were incorporated into these granules that were isolated by differential centrifugation. These particulate factors (PFs) were able to transfer, in a dose- and time-dependent manner, appreciable levels of therapeutic genes, related proteins, and drugs. Thus, when recipient cells of SG-carrying PFs were exposed to ganciclovir, this prodrug was efficiently activated, eliminating them. These PFs kept the functionality of their cargo, even after being subjected to adverse conditions, such as the presence of DNase, freezing, or heating. Since our in vitro system did not include any of the immune mechanisms that could provide additional antitumor activity, the chemo-gene treatments amplified by these delivery bags of therapeutic agents offer a great clinical potential.
Insights
Melanoma cells release therapeutic granules after treatment. These "particulate factors" deliver genes and drugs to kill cancer cells, showing promise for new cancer therapies.
Area of Science:
- Comparative oncology
- Cancer cell biology
- Gene therapy
Background:
- Companion animal melanoma cells serve as valuable models for human cancer research.
- Understanding cellular responses to therapeutic agents is crucial for treatment optimization.
Purpose of the Study:
- To investigate the therapeutic potential of particulate factors released from melanoma cells undergoing treatment.
- To evaluate the gene and drug delivery capabilities of these particulate factors.
Main Methods:
- Treatment of human, canine, and feline melanoma cells with bleomycin, interferon-β, or herpes simplex virus thymidine kinase/ganciclovir suicide gene (SG) therapy.
- Isolation and characterization of released nano- and micro-sized granules (particulate factors) using transmission electron microscopy and differential centrifugation.
- Assessment of the therapeutic gene and drug transfer efficiency and functionality of particulate factors in recipient cells.
Main Results:
- Treated melanoma cells showed increased granularity and released particulate factors containing therapeutic transgenes and proteins.
- Particulate factors effectively delivered functional genes and drugs to recipient cells, enabling prodrug activation and cell elimination.
- The therapeutic cargo within particulate factors remained functional even after exposure to DNase, freezing, or heating.
Conclusions:
- Particulate factors derived from treated melanoma cells represent a novel delivery system for chemo-gene cancer therapy.
- These findings highlight the potential clinical application of amplified therapeutic agents encapsulated in delivery vesicles for cancer treatment.
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