Understanding How Hypoxia Alters the Breast Cancer Proteome in the Context of Molecular Subtypes and Metastatic Organotropism
Abstract
Breast cancer is a leading cause of cancer diagnosis and death in Canadian women, with >90% of deaths caused by metastasis. The current study explores how hypoxia affects cancer aggressiveness and metastatic potential across breast cancer cell lines representing different molecular subtypes and those that metastasize to different organs. Using liquid chromatography with tandem mass spectrometry (LC-MS/MS), comparison of normoxic and hypoxic proteomes of different breast cancer cell lines revealed changes to pro-survival and metastatic mechanisms contributing to subtype-associated aggressiveness. We also identified that extracellular exosomes and associated integrins are significantly upregulated components of the hypoxia response, suggesting their role in metastasis, especially to bone. Additionally, 8 clinically significant hypoxia-enriched proteins were identified specific to triple negative disease outcomes. Overall, hypoxia mediated subtype-specific aggressiveness and metastatic behavior, potentially via extracellular exosomes. This research offers insights into subtype-specific differences and identifies potential therapeutic opportunities to mitigate breast cancer metastasis in the future.