Advanced stages of cancer often involve the spread of cancer cells from the primary tumour to the rest of the body via the circulatory system to form secondary tumours called metastases. Metastatic disease has a poor prognosis as they are hard to treat and often directly responsible or involved in cancer patient deaths. To date, researching how cancer cells navigate through the circulatory system, including small blood vessels, has been very difficult. This is because cancer cells travel within approximately 60,000 miles of blood vessels, often as very small clusters or even single cells that are just a few micrometres (millionths of a meter) in size; it’s like trying to find a needle in a haystack.

Julia Perea Paizal, PhD student in the laboratories of Dr Sam Au at Imperial College London and Professor Chris Bakal at the ICR, used a mixture of microfluidic engineering and cell biology to mimic human capillaries to investigate how the biomechanical forces associated with small blood vessels affect cancerous and non-cancerous breast cells as they travel through these small spaces.

Their findings interestingly suggest that non-cancerous cells travelling through a small capillary are susceptible to triggering an inflammatory response whereas cancerous cells making the same journey do not. This could be because cancerous cells have already undergone changes through a phenomenon called the epithelial–mesenchymal transition which may render them less susceptible to capillary constriction forces. This absence of inflammatory response could be linked to an avoidance of immune detection, making them more likely to re-settle undetected in a new location. On the other hand, forces associated with small blood vessels triggered cancer like traits in non-cancerous cells.

Understanding the underlying mechanisms and steps involved in early stages of metastasis is crucial to be able to target their formation and improve patient outcomes in many cancer types.

Read the full paper for more information. 

“I find it fascinating that constriction forces alone triggered metastatic traits in non-malignant cells, while metastatic cells were less affected when squeezing through capillaries as they have already transited through them during their metastatic journey and probably adapted. I am excited about the possibility of targeting the adaptations that these cells undergo while in the circulation to reduce their potential to colonise distant organs.” 

      Julia Perea Paizal