A mammary gland mast cell tumour.
Credit: iStockPhoto
~ Upulie Divisekera
The pulpy, flesh coloured lump lay in front of me in the dish. This was a new one. I'd never had to process a tumour sample before. Studying breast cancer (or any cancer) requires models, or proxies, so that we can dissect out what is happening in the cell.
I'd always used existing models. But this is where they always start. A lump of cells that, if left in the body, would have continued growing out of control. How could I take this three-dimensional tissue and turn it into a layer of cells that I could easily grow and manipulate? I needed to be able to pull out the tumour cells from all the other kinds of cells in that lump - the connective tissue, the blood vessels.
It was actually pretty easy. Crude, even. I had a fine pair of scissors, and I cut the tumour, julienned it as finely as I could in a solution of nutrients, or medium. This is what we use to grow cells in on an everyday basis in the lab, but this media had the added ingredient of collagenase, an enzyme which would help break down collagen, the protein that is the main component of connective tissue. This would help pull the cells apart chemically as well as physically.
After incubating this mix of cells in this solution, I mashed the cells through a tiny sieve. At a mere 70 micrometres long (70 millionths of a metre), the holes were tiny. This would get rid of the larger lumps of calls that I hadn't managed to break down. So I had a tumour cell mash. The cells were put into a plastic flask, which is the modern day Petri dish, and then the waiting began.
Most of the non-tumour cells would die off over time, as the medium didn't have specific growth factors and nutrients that they needed to survive. The hope is that all that would be left is the tumour cells. And that's the hallmark of the tumour cell: it survives. It doesn't need special growth factors or hormones to survive, it just needs nutrients. It is pure, undifferentiated tissue - masses of fast-growing, out of control cells. And the cell 'line' that came from this tissue could be used to study the specific kind of breast cancer we were interested in.
Cell lines are an important part of biological research. They allow you to test a bunch of ideas and theories in a convenient plastic dish. You can test the effects of potential drugs, attempt to understand which genes are important for the cancer to survive, and which genes are expressed in abundance - a phenomenon scientists call 'over expression'. All cancers are unique, but some of them can be grouped according to what genes they over express - or that are under expressed. In breast cancer, we have so far discovered three identifiable kinds of cancer, each expressing a particular profile of different genes. Knowing what genes are expressed helps scientists to work out what to target when they were trying to find drugs that would kill the cancer cells. It helps to have a target.
Our tumour model over expressed a gene called epidermal growth factor receptor 2, also known as Her2Neu. This gene is commonly over expressed in one set of breast cancers, and it has a unique drug targeted to it called Trastuzumab, or Herceptin. This is a novel therapy unlike most cancer drugs, which are chemicals that kill all fast-growing cells. Herceptin, on the other hand, is an antibody, so it is a drug that is specifically targeted, in this case to Her2Neu. It harnesses the power of the immune system to target the tumour. So instead of just hitting all cancer cells and any other rapidly growing cells with chemotherapies, it targets the Her2Neu over expressing cells, and targets them more effectively.
Herceptin has been in the clinic for some time. We've been studying the effect of Herceptin on Her2Neu tumours, trying to dissect out what molecular pathways it affected to help kill the cancer cell, which immune cells it recruited to help. By understanding what these pathways and cells are, we can potentially find other possible targets to generate therapies for.
So far, our work has indicated that another antibody therapy, when used with Herceptin, could be used to treat Her2Neu tumours. The combined effect of these therapies seemed, oddly, to be greater than the sum of its parts. This was an exciting discovery because it meant that we could try combining therapies for treating patients, potentially enhancing existing treatments, and increasing the specificity of treatments for each cancer. We could even combine antibody therapies with therapies like chemotherapy to really try to knock the tumour out.
For centuries, breast cancer has been a mystery we couldn't unravel. Now, with tools like these, we have the means to dissect this disease, pull it apart like a circuit. It's a long, slow process, but it all starts with a lump of cells in a Petri dish.
