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The Crosstalk between HepG2 and HMC-III Cells: In Vitro Modulation of Gene Expression with Conditioned Media
Prashant Koshal1, Ilenia Matera1, Vittorio Abruzzese1
1Department of Sciences, University of Basilicata, 85100 Potenza, Italy.
Abstract:
Epidemiological studies have postulated an inverse correlation between developing cancer and neurodegeneration. It is known that the secretome plays a vital role in cell-cell communication in health and disease; the microglia is the resident macrophage of the central nervous system which maintains neuronal integrity by adapting as the microenvironment changes. The present study aimed to identify, in a cell model, biomarkers that link neurodegenerative diseases to cancer or vice versa. Real-time PCR and western blot analysis were used to characterize the effects on gene and protein expression of human hepatoblastoma (HepG2) and human microglia (HMC-III) cells after exchanging part of their conditioned medium. Biomarkers of the endoplasmic reticulum, and mitophagy and inflammatory processes were evaluated. In both cell types, we observed the activation of cytoprotective mechanisms against any potential pro-oxidant or pro-inflammatory signals present in secretomes. In contrast, HepG2 but not HMC-III cells seem to trigger autophagic processes following treatment with conditioned medium of microglia, thus suggesting a cell-specific adaptive response.
Insights
This study explored biomarkers linking cancer and neurodegeneration using cell models. Human hepatoblastoma and microglia cells showed adaptive responses, with cancer cells activating autophagy when exposed to microglia secretomes.
Area of Science:
- Neuroscience
- Oncology
- Cell Biology
Background:
- Epidemiological studies suggest an inverse relationship between cancer and neurodegenerative diseases.
- The secretome, released by cells, is crucial for intercellular communication in physiological and pathological states.
- Microglia, the central nervous system's resident immune cells, are vital for neuronal health and adapt to environmental changes.
Purpose of the Study:
- To identify biomarkers connecting neurodegenerative diseases and cancer using a cell-based model.
- To investigate the cross-talk between cancer cells and microglia via their secretomes.
- To understand cell-specific adaptive responses in the context of potential disease links.
Main Methods:
- Utilized human hepatoblastoma (HepG2) and human microglia (HMC-III) cell lines.
- Exchanged conditioned media between HepG2 and HMC-III cells.
- Employed real-time PCR and western blot to analyze gene and protein expression.
- Evaluated biomarkers related to endoplasmic reticulum stress, mitophagy, and inflammation.
Main Results:
- Both cell types activated cytoprotective mechanisms against pro-oxidant or pro-inflammatory signals in exchanged secretomes.
- Human hepatoblastoma cells, but not microglia cells, initiated autophagic processes upon exposure to microglia-conditioned medium.
- Observed cell-specific adaptive responses, indicating differential reactions to intercellular signaling.
Conclusions:
- The secretome mediates complex intercellular communication relevant to cancer and neurodegeneration.
- Cancer cells exhibit unique autophagic responses to microglia signaling, suggesting distinct adaptive strategies.
- Findings provide insights into potential molecular links and cell-specific adaptations between cancer and neurodegenerative disease pathways.
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