Abstract: PD65-02
Sources of Funding: Prostate Cancer Canada, OICR, AMOSO, CUOG

Introduction

Tumor cells acquire qualities that enable them to succeed at key steps of the metastatic cascade, but very little is known about how individual cells accomplish these feats in a challenging hemodynamically active environment. Using intravital imaging, we observe that oncosome release is a key event during cancer cell extravasation in various prostate cancer cell lines. Oncosomes are large cell fragments released by cancer cells at various stages of cancer progression. Having observed their release in vivo during cancer cell extravasation, we sought to determine at what other stages of metastasis oncosomes were released. _x000D_ _x000D_

Methods

Using PC-3, LnCAP, Du145 cells, intravenous injection into the chorioallantoic membrane (CAM) of chick embryos, a gold standard of visualizing cancer cell extravasation, was employed and confocal resonance scanning microscopy was used to visualize the release of oncosomes and other smaller extracellular vesicles in vivo. Blood at various timepoints was also collected to enumerate the number of CD9+ve and STEAP1+ve oncosomes released by extravasating cells. Primary tumors were also formed and blood collected in the same manner to ascertain the extent of oncosome release in vivo.

Results

At the key step of extravasation, arrested cancer cells release oncosomes into the microcirculation which are observed to exhibit a diameter >900 nm and expressing surface antigens found on the surrogate prostate cancer cell such as CD9 and STEAP1. We explored the abundance and biophysical characteristics (size diameter range) of extracellular vesicles (EVs) released during the metastatic cascade and found that oncosomes are not consistently released by primary tumors or metastases and that these large cancer cell fragments are specifically released by actively extravasating cancer cells.

Conclusions

Circulating oncosome levels in patient plasma are a novel biomarker or “liquid biopsy� for actively metastasizing cells in the body, representing a powerful tool for monitoring metastatic cancer dynamics. We show that oncosome biogenesis is a specific byproduct of extravasating cells and not by primary tumors or metastatic deposits even in the presence of pro-apoptotic or pro-necroptotic stimuli. Our findings in plasma samples from patients on first-line treatment for metastatic prostate cancer support the concept of oncosomes as a promising biomarker for monitoring cancer metastasis dynamics in real-time, a novel &[Prime]liquid biopsy&[Prime] for metastatic prostate cancer treatment response.

Funding

Prostate Cancer Canada, OICR, AMOSO, CUOG