Colon cancer research – Dr Clement Penny
- Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand
- Email: Clement.Penny@wits.ac.za
Title of the project
Isolation and characterization of colon cancer stem cells: the effects of epigenetic modulation on pluripotent markers
Highlights of the project
Background: Cancer stem cells have been identified in a number of solid tumours. As they are associated with resistance to chemotherapy and radiation therapy, they remain as a distinct living cell population able to cause disease relapse, giving rise to new tumours. We have detected and isolated colon cancer stem cells in the HT29 and DLD-1 colon cancer cell lines and are testing novel therapies against these cells. Targeting and destroying the stem cells will lead to improved survival and quality of life of cancer patients.
Main Objective: The identification and isolation of a colorectal cancer stem cell population; assessment of the effects of novel DNA modifying (epigenetic) drugs on these cancer stem cells.
Colorectal cancer stem cells; identification and isolation:
We have isolated and cultured colon cancer stem cells such as those that occur within colorectal cancer. This is an important population of cells that give rise to solid tumours and are able to grow excessively. Also, they are believed to responsible for patient relapse and renewed tumour growth, since they are able to escape radiation therapy and chemotherapeutic treatment.
Currently, this study has investigated the presence of such cancer stem cells within a number of different colon cancer cell lines, representing early and later stages of colon cancer. As the cancer stem cells produce a unique protein, called CD133, allowing for their identification from the surrounding cells lacking the protein. The cancer stem cells also produce other proteins called Oct 3/4, Sox2 and Nanog. These three proteins are associated with other types of stem cells, including embryonic stem cells.
It is also shown here that cell lines similar to early stages of colon cancer have few stem cells. In contrast however, the cell lines comparable to late stage metastatic colon cancer have large percentages of stem cells (up to 50 %), producing the stem cell protein. This finding may be an important observation for potential treatments, wherein the stem cell populations need to be eliminated, to prevent tumour recurrence and metastasis.
Methylation patterns, cancer and stem cells:
An important way of coding DNA is via the addition of methyl groups to DNA; different amounts of such methyl groups give cells different identities, and in particular, stem cells. This process of methylation is called an epigenetic modification of cellular DNA. What is also of importance is that these epigenetic changes respond to environmental factors, for example stress, or toxins, which can then directly change the expression of genes, so eventually leading to cancer over a period of time. Typically, unusual DNA methylation patterns are associated with many human malignancies.
American Society for Cell Biology, Dec 3rd –Dec 7th 2011, Denver, Colorado. The HT29 and DLD1 colorectal cancer cell lines contain cancer stem cells. C.B. Penny, B.L. Milner, V. Gibbon and P. Ruff.