DIPG Dialogue

Dr. Maryam Rahman

June 2009

Introduction:

Dr. Maryam Rahman is a research fellow in Dr. Reynolds’ lab at the University of Florida. Dr. Rahman is also a 4th year neurosurgery resident with a strong interest in neuro-oncology and novel therapy development. She has been responsible for BMP receptor/pathway activation experiments and the application to the NIH and FDA for testing of BMP 4 in human malignant glioma.
Dr. Rahman’s research on BMP4 and cell lines has recently been funded through a collaborative effort within the United Forces Against Brain Tumors. Just One More Day along with Gunner’s Magic Train and the Musella Foundation joined together to support her research. BMP4 has been shown to cause human glioblastoma cancer stem cells to become end cells that have a limited number of cell divisions and are more easily killed. The question is whether this effect can occur with other types of glioma cells.

Questions & Answers:

Where do you get cancer cell lines from?

Cancer lines are created by taking fresh tumor tissue from a surgical specimen. This tissue is dissociated into single cells and then placed in culture with growth factors. These cultures are placed in an incubator at 37 degrees C (like all cultures) and nurtured with media and growth factors until they start proliferating. Once the cells start proliferating, after several days, they outgrow their culture flask and need to be "passed" which means that they are dissociated into single cell suspension. Some of these cells are placed in a new flask with media and growth factors. The other cells can also be placed in culture (to expand the number of cells you produce) or used for experiments. Here at the University of Florida, we obtain our tumor tissue from the Florida Center for Brain Tumor Research. They obtain consent from the patients pre-operatively. Tissue is collected intra-operatively and given to us for cell culture and experimentation.

Would each individual's tumor grow out a different type of cell line?

Absolutely. Every patient's tumor is unique and therefore, having multiple lines of a type of tumor is beneficial for experimentation. Even within a certain type of tumor, there is variation in behavior and response to drugs.

Why does one use a cell line?

Cell lines are useful because it gives you an endless supply of tumor cells to use for experiments. If the cells we obtain from tumor tissue are fixed and used immediately for experimentation (which we do if we have a lot of cells and have some left over after placing them in culture), it could only be used once. The cell lines allow us to experiment with the tumor indefinitely.

Are cell lines stable or do they change over time?

Cell lines do not usually change over time. However, culture conditions do select out certain cells that can grow in media and growth factors. Therefore, cell lines are not always completely representative of the original tumor. This is the biggest argument against cell line work. I think cell line work is an important first step in understanding tumor biology, but it has to be supplemented and followed by animal and finally human work.

If there is a biopsy is there enough tissue to do what is needed therapeutically and perhaps to grow out a cell line?

Unfortunately, there is usually not enough tissue from a biopsy to do anything other than pathologic analysis. We only get tissue that is given to us after the pathologist takes what is necessary for diagnosis.

Dr. Rahman, you are saying that there are no cell lines of diffuse intrinsic pontine gliomas. Since we do not have cell lines but we have had biopsy and autopsy tissue which show most of these tumors to be gliomas , but not all GBMs, then it could follow that it might be important to find an agent that works on a wide variety of gliomas to try to cure DIPGs?

I do think that experimentation using other low grade glioma cell lines may be relevant to the treatment of DIPGs. You are absolutely correct with that question. I think that's why it's important to experiment with BMP in gliomas other than GBM.

References-

Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006 Dec 7;444(7120):761-5

BMPing off glioma stem cells. Cancer Cell. 2008 Jan;13(1):3-4