Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles

A recent paper by the University of California, published in Frontiers in Cell Developmental Biology, delves into the field of cancer cell biology. Employing the cutting-edge Zetaview ® Nanoparticle Tracking Analyser (NTA) instrument, the study examines cellular dynamics, shedding light on the mechanisms underlying tumour progression, metastasis, and therapeutic resistance. This innovative approach allows researchers to observe and quantify the behaviour of nanoparticles within cancer cells, providing invaluable insights into the molecular pathways driving malignancy. Through the utilisation of Zetaview® NTA, the University of California’s paper contributes significantly to the expanding field of cancer research, paving the way for novel therapeutic strategies and diagnostic tools.

Prostate cancer (PCa) is a common cancer in men, often spreading to the bones with limited treatment options. Research has shown that extracellular vesicles (EVs) play a crucial role in the spread of certain cancers, by creating supportive microenvironments in separate areas of the body. Studies have shown that PCa EVs help cancer to metastasize to the bone. However, it’s unclear how these EVs affect the osteoblasts early on. In this study, PCa EVs were isolated and then repedetly injected into mice twice a week over a period of 4 weeks to mimic how they spread from the primary tumour. The results showed that these EVs accumulated in the liver and spleen within 24 hours, in the lungs after 2 weeks of explosure and in limb bones and lymph nodes following 3-4 weeks of explosure. The accumulation of the EVs in the limb bones caused molecular changes in the bone. These changes distrupted normal bone functions, specific pathways like Paxilin, Estrogen Receptor, RHOA, Ribonucleotide reducaste, and ERK/MAPK were shown to be involvd in these chnages. In vitro tests on human osteoblasts confirmed these findings. Additionally, comaparing gene signatures revealed similarities with osteocytes, suggesting their involvement. No visible bone changes were detcted indicating the impact of PCa EVs was at a molecular level. Understanding these early events could lead to targeted treatments to stop prostate cancer metastasizing to the bones.

While conducting this research, EV’s were chracterised by Brownian motion using Particle Metrix ZetaView nanoparticle tracking analysis instrument. The EV’s were also classified using electrophoresis and visualised by transmission electron microscopy.

Particle Metrix ZetaView™ 

The ZetaView® is a unique Nanoparticle Tracking Analysis (NTA) instrument for measuring hydrodynamic particle size, concentration, fluoresence, colocalisation and zeta potential.

Key Features:

• Scanning NTA
• Fixed cell assembly design
• Increased fluoresence capabilities
• Colocalisation measurements
• Auto-alignment & auto-focus
• Sample recovery
• Fast measurements
• Quick and simple cleaning