Poster T1 - Cancer Cell Spheroid Response to pH and Hypoxia in the Tumor Microenvironment

Introduction: The rapid growth of cancer tumors often outpaces vessel formation, resulting in insufficient oxygen supply. This triggers the expression of hypoxia-inducible factor (HIF), prompting metabolic shifts towards glycolysis. Inadequate vascular networks also hinder the removal of acidic byproducts, leading to extracellular acid accumulation. Evidence suggests that these conditions may contribute to the emergence of cancer cell subpopulations with aggressive traits, such as increased proliferation, invasion, and therapy resistance.

Materials and

Methods: This study aims to investigate the effects of hypoxia and acidosis on long-term cellular behavior and to elucidate the mechanisms contributing to hypoxic and acidosis-induced malignant behavior. Controlled variations in media pH and hypoxic conditions were applied to 3D MDA-MB-231 and MCF-7 breast cancer spheroids, simulating tumor microenvironments. The growth of tumor spheroids was tracked through live cell imaging over 30 days to elucidate the impact of extended acidosis and hypoxia on cellular proliferation. At specific time points during growth tracking, spheroids were harvested for subsequent immunohistochemistry and RT-qPCR analysis.

Results, Conclusions, and Discussions: Experiments indicate that cancer cells exhibit suppressed initial growth in hypoxic and acidic conditions compared to neutral and normoxic conditions. However, cells later adapted and exhibited increased proliferation rates in a pH-dependent manner (Figure 1A & 1B). Results also indicate that exposure to acidic and hypoxic conditions over time lead to alterations in the expression of proliferation and metastatic cell markers. These findings highlight cancer cell adaptation and malignancy to different pH and hypoxia conditions.

Acknowledgements (Optional):