Secretomics reveals hormone-therapy of breast cancer may induce survival by facilitating hypercoagulation and immunomodulation in vitro

Abstract

Tumour cell haematogenous dissemination is predicated on molecular changes that enhance their capacity for invasion and preparation of the pre-metastatic niche. It is increasingly evident that platelets play an essential role in this transformation. The systemic nature of signalling molecules and extravascular factors that participate in mediating platelet-tumour cell interactions led to the development of an in vitro co-culture using whole blood and breast tumour cells, allowing us to decipher the impact of hormone-therapy on tumour cells and associated changes in the plasma proteome. Using mass spectrometry, we determined dysregulation of proteins associated with maintaining an invasive tumour phenotype. Tumour changes in genes associated with EMT and survival were documented. This is postulated to be induced via tumour cell interactions with the coagulatory and immune systems. Results highlight tumour cell adaptability to both treatment and blood resulting in a pro-tumorigenic response and a hypercoagulatory state. We illustrate that the breast cancer cell secretome can be altered by hormone-therapy, subject to the tumour subphenotype and linked to platelet activation. More sophisticated co-culture systems are required to recapitulate these interactions to better understand tumorigenesis. Moreover, deeper plasma profiling, using abundant protein depleted and/or vesicle enriched strategies, will likely reveal additional secretory proteins related to tumour cell-platelet interactions.