Wednesday, March 11, 2009

Mets are Vets?

The other day I was talking to one of my advisers and he mentioned that a reviewer had just critiques the fact that the Acid Mediated Tumor Invasion does not consider the fact that the aggressive cells selected by tumor microenvironment (hypoxic and acidic) should lose this phenotype once they progress through healthy tumors, since the selective pressure on these cells decreases as they invade further from original tumor.
A metaphor used by that time was that tumor cells are like Navy Seals who, once far from their training environment, relaxing in a paradisaical beach would eventually get soft like other regular people.
The point here, I believe, is that the metaphor is wrong for tumor cells are not trained to be tough, they are selected, they are traumatized like 17-year old boys who are sent to war. Those who are able to adapt, to toughen up, survive and come back home, but many of them cannot adapt back to normal life.
The perfect example is John Rambo. When Rambo, and many other Vietnam war vets, returned to US, he no longer could live in society as we do. He would see threats everywhere, he would trust no one and would not accept the authority of civilians. In the movie Rambo escapes from prison and hides in the woods nearby the city. When the police and National Guard try and capture him he turns back to the Green Beret M.O. and kills them all.
At the end of the movie he destroy much of the city including the Police Station.
I believe that the cells that survived the stress created by tumor development and reached a more healthy environment to live will, in their majority, settle down. The cells that start new metastases however are like John Rambo: they cannot re-adapt to normal environment so they tend to re-create the original environment that traumatized them.
If this is true, there may be ways of acquiring an aggressive phenotype through reversible ways (most of tumor cells) but some of these ways may yield to irreversible conversion and eventually lead to cells that can generate metastases.
A microarray analysis as well as protein expression of cells recovered from metastases compared to the original tumor cells might yield to clues on how this commitment happens.


Blogger David Basanta said...

Hi Ariosto,
I know that this is not precisely a new post but I was revisiting your blog and thought I'd post the following comment.

I really like your comparison of agressive tumour cells with Rambo and how that might explain why cells grown in an acidic environment don't change their behaviour once they reach a properly oxygenated region. Still, when it comes to evolutionary pressures we would not be requiring the tumour cell to change (although who knows whether they can?) but the offpsring of that cell. Using your metaphor it would suggest that the children of Rambo would still be traumatised.

It would also imply that if the offspring is heterogeneous there is no selection pressure in favour of those that can re-adapt to the non hypoxic environment.

I believe (and I bet so does Bob Gatenby) that the reason they don't change is not only because they can't change but mainly because they don't have any reason to change. They were good fighting the Vietnamese and they are good fighting the local police as well and that's what they want to do, fight, conquer and grow. The acid resulting from the glycolitic metabolism is their weapon!

10:16 PM  

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