Researchers at Okayama University have successfully created a mouse model suitable for studying the behaviour of cancer stem cells (CSCs) in tumours.

Their initial insights clarify the role taken by CSCs in promoting tumour vasculature in the early stages of tumour growth.

In order to grow beyond a certain size, tumour cells trigger angiogenesis – a process by which new blood vessels form existing vessel structures.

The tumour cells activate multiple mechanisms to develop blood vasculature, which then provides the tumour with the oxygen and nutrients it needs to grow.

While the basic processes surrounding tumour growth is reasonably well-understood, there is growing evidence to suggest that the formation of the vascular network is not restricted to angiogenesis.

In fact, cancer stem cells (or CSCs) - cells within the tumour that can self-renew and differentiate into different cell types - appear to contribute to a phenomenon called ‘vasculogenic mimicry’; the formation of vascular-like channels without usual input from endothelial cells (common tissue cells) and growth factors.

Now, Professor Masaharu Seno and co-workers at Okayama University, together with scientists across Japan, China and the US, have generated a mouse model for assessing the role of CSCs in cancerous

Their results give considerable insights into the process of vasculogenic mimicry and may inform future therapeutic strategies.

The team had previously established their mouse model, miPSC-LLCcm, using mouse-induced pluripotent stem cells.

They introduced the DsRed gene into the model which emits red-colored fluorescence and allowed the team to track CSCs during tumour growth.

They found that angiogenic growth factors were predominantly expressed in one population of CSCs.

This CSC group also worked to recruit endothelial cells from the host and promote the maturation of endothelial cells differentiated from the CSCs themselves.

Seno’s team then discovered that the remaining undifferentiated miPSC-LLCcm cells were directly involved in the formation of vasculogenic mimicry.

These results indicate that tumour vasculature is a vital part of tumour growth, and highlights why therapies that solely target angiogenesis are not working as well as expected.

As Seno states in their paper , published in The American Journal of Cancer Research, “miPSC-LLCcm could be an appropriate model to understand entire tumour vascularization and to develop novel drugs and therapeutic strategies.”

Tumours cannot grow very large without help from their host body.

To survive and grow, tumour cells initiate the process of angiogenesis – creating new blood vessels from the existing tumour vessel structures.

Inflammatory proteins and angiogenic factors are released by the tumour cells, which activates endothelial cells (common tissue cells found all over the body) and triggers degradation at the base of the tumour.

This allows the endothelial cells to invade the surrounding membrane, multiply and migrate to form new blood vessels.

Despite this knowledge of growth influenced by angiogenesis, cancer therapies targeting angiogenesis alone have not been particularly successful.

Seno and his team at Okayama University sought to clarify the role of other cancerous cells within the tumour – self-renewing cancer stem cells (CSCs) – to see if they also contribute to tumour vascularization.

The team’s results suggest CSCs are heavily involved in vascularization, both through recruiting endothelial cells from outside the tumour and differentiating into endothelial cells themselves.

Further, the undifferentiated CSCs go on to mimic the formation of blood vessels, creating new vessel-like structures without the aid of other proteins and growth factors.

Seno’s team believe their results suggest further investigations are needed into CSC behaviour in tumour cells, and that their mouse model (miPSC-LLCcm) will provide scientists with the means to conduct these studies.

They hope that their model will inform future targeted therapies for cancer.

Source: The American Journal of Cancer Research