Cancer Stem Cells Lessons Learned from Glioblastomas

By: AHAScienceNews

- So my name is Inder Verma. I am a professor at the Salk Institute in La Jolla. I've been there for the last four decades, and I am the keynote speaker today. And my subject in your discussion today is stem cells, cancer, by using glioblastoma as an example. So what are stem cells in cancer? Cancer stem cell is a cell, which exists in a cancer, which has the ability to continuously replicate and proliferate and they'll have the ability to differentiate to all the lineages that are present in that particular tissue. So, in the case of the brain one would understand to think of the cancer stem cell as a cell, which can continuously divide, and also go on to make the major cell types in the brain, like the neurons, oligodendrocytes, and for example, glials. So, the amazing thing about glioblastoma is that every patient who has unfortunately GBM undergoes surgery at some point to remove the big burden of the tumor, but almost 100% is guaranteed that the tumor can come back.

And sometimes the tumors come back within days, and months and weeks. Sometimes it takes a bit longer. Sometimes they come during the treatment, like radiation that is given to the patient after that.

So it is remarkable, how every cell... In the brain tumors, regardless of how much surgery, how good the surgery is done it will come back again and make the tumor. So how did a terminally differentiated cell that is present in the brain, like neurons, they don't divide, glial cells, or oligodendrocytes.

How do they go on to become a cancer stem cell? What I'm going to point out is that when there's an alter genetic consult, meaning that there are genes which have the ability to cause cancer get into all these cells and as a mutation undergo the mutation, it then de-differentiates or reprograms the terminally differentiated cell back into stem cells. After all, a neuron or a glial, or an oligoendrocyte originated from the stem cell. And what has cancer done to them is that when alter genes are mutated, or undergo a change, they reprogram or de-differentiate back into a stem cell. And if you recall, that is now a very well accepted fact, what we call the IPS technology, where a terminally differentiated cell can go on to become a stem cell and in fact some cases, they can then go on to become any cell type in the body.

Cancer Stem Cells Lessons Learned from Glioblastomas

So, what I want to emphasize in my talk is that this is a remarkable situation where we now understand how glioblastoma are formed. So now that we know, our job is to prevent these cells to either prevent them to differentiate, or to continuously proliferate. So not only that..., we discovered something else along with it.

And that was that the brain is highly vascularized. In fact, it's probably the most vascularized organ in the body not surprisingly because it's continually functional, needs metabolism, needs food. So why not try to block blood vessels going to the tumor? Because that would not take the food, and therefore the tumor will die. But unfortunately, that didn't work.

Because what happened is these tumors... Actually dysfunctional transdifferentiated to become a blood vessel. So normally you have a process of blood vessels, and you can use inhibitors which prevent the formation of blood vessels, but these tumors actually went on to become blood vessels in a different manner by which all the inhibitors of blood vessels were ineffective. So the tumors are pretty smart because they only had one thing to do in their life, to grow. So not only their growth, they also transdifferentiate. So I am trying to talk in my keynote address how this process functions, what's the importance to understand the biology of cancer, how we can take advantage of this for the very fact by which the tumor actually becomes malignant, also offers us the achilles heel that we can stop the malignancy by letting it grow, or to differentiate, or to transdifferentiate. So that's what I'm trying to bring together, and how basic biology of understanding stem cells can eventually lead us to understand how cancers are formed and eventually therapeutics, which of course have wider implications.

Because all cells in one way or the other, have the origins of stem cells. So by understanding this principle, we actually also understand other principles of stem cells including cardiomyocytes, phagocytes in muscle cells, and of course they also then offer us the opportunity to see the progression of the disease, because the technology we do up here are the same technology that can be used for other things for example a cerebral tumor from cerebral hemorrhages, and other types of diseases that connect to the brain. So that will be the general thing that I will be talking about.

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