Cancer stem cells
Background
When a normal cell divides, it produces two identical daughter cells. When a cancer stem cell divides, it produces a new cancer stem cell and a differentiated cell, which grows to form the tumour mass. The stem cells are the most important source of secondary growths and, unlike the tumour mass, are generally resistant to conventional chemotherapy (see illustration).
Early detection and eradication of the new resistant stem cells is therefore vital to increase a patient's chances of survival.
Aims
1. To develop therapies to eradicate cancer stem cells.
2. To see whether positive tests for blood stem cells indicate risk of secondary tumours (metastases) so that more aggressive treatment can be instigated.
The project
Through our research we intend to isolate and so detect any stem cells in the blood and in primary tumour tissue excised during a patient's operation. This will be done by targeting tumour cell surface markers, using a powerful antibody directed against 'c-Met' produced by the Belgian company arGEN-X. This antibody has been shown to inhibit the growth of human tumour grafts, and to kill the stem cells within them by recruiting the help of two different factors in blood, 'complement' and/or white blood cells (known as 'natural killer cells').
In addition to researching detection, we will grow the stem cells and test the survival of the progeny cultured again with the c-Met antibody. As a back-up, we will also test with tiny gold nanoparticles developed by Midatech Ltd – coated with epithelial growth factor or folic acid to get the particles into the cells – alongside small drug inhibitors of c-Met or conventional chemotherapy drugs. We will compare the effects on newly-generated stem cells and any differentiated tumour cells.
We will also compare the stem cells with their parent tumour cells for their ability to penetrate a human skin model, as an indicator of metastatic potential.
Dr. T. Lund, Research Associate – Isolation and killing of stem cells
Dr. Song Wen, Research Associate – Growing and identifying cancer stem cells
Clinician, Imperial NHS Trust & St. George's Hospital – Provision of clinical material
