# Transcriptomic Alterations of Canine Histiocytic Sarcoma Cells in Response to Different Stressors

## TL;DR

This study explores how canine histiocytic sarcoma cells respond to hypoxia and starvation, revealing significant gene expression changes that could inform future cancer treatments.

## Contribution

The study identifies specific gene expression alterations in canine histiocytic sarcoma cells under hypoxia and starvation, highlighting potential therapeutic targets.

## Key findings

- Short-term hypoxia upregulates genes related to vasculature development and downregulates cell cycle genes.
- Prolonged hypoxia and starvation induce distinct gene expression patterns, including immune responses and adhesion.
- Lipid metabolism and cell cycle pathways are downregulated under prolonged hypoxia and starvation, respectively.

## Abstract

Canine histiocytic sarcoma (HS) is a rare tumor with a poor prognosis. Rapid tumor growth often causes central hypoxia and starvation, impacting tumor progression. In the present study, HS cells were cultured under hypoxia and starvation for 1 and 3 days, simulating intermediate and central tumor zones, respectively. Cells were counted at each time point, followed by RNAseq analysis. Only hypoxia significantly reduced the cell number (p < 0.05). Short-term hypoxia altered 1645 differentially expressed genes (DEGs). Upregulated genes belonged to vasculature development, and downregulated genes to cell cycle processes. Short-term starvation affected 157 genes, mainly involving responses to stimuli. Prolonged hypoxia and starvation induced 1301 and 836 DEGs, respectively. Prolonged hypoxia upregulated genes mainly involved in immune responses, response to stimulus, adhesion, and angiogenesis. Prolonged starvation upregulated genes associated with signaling, adhesion, circulatory system development, and response to stimulus. Lipid metabolism and cell cycle pathways were downregulated under prolonged hypoxia and starvation, respectively. KEGG “pathways in cancer” were enriched under all conditions (adjusted p-values < 0.05). These findings indicate that hypoxia and starvation significantly alter the expression of genes involved in tumor progression. Further studies, namely post-translational analyses, are needed to elucidate the functional impact of these changes and identify potential therapeutic targets.