Thread: Mortal cancer cells ?

Hi, and sorry for my English. I have a problem understanging the following article http://www.chirurgiewien.at/wp/wp-co...e-EJC-2008.pdf

In this article, 8 cell strains derived from patients with medullary thyroid carcinoma are used.
All strains except one have a low telomerase activity, their telomeres shortened each time they replicate, and then they stop dividing after a certain number of division. Only in rare cases spontaneous immortalised cells arise when the experiment is conducted several times.

I really don't understand that. If thoses cells are mortal, they aren't cancer cells no ?

Have a nice day

Interesting paper. I understood cancer cells the same way you do.

The cells are still expressing telomerase, just at a much lower rate than most cancer cells. As i understand it (not particularly well) cell immortalisation occurs in a pre-cancerous state which helps the cell accumulate more mutations thereby becoming cancerous. Perhaps the little telomerase present here is enough for the medullary thyroid cells to acquire enough mutations. The authors still conclude lowering telomerase is a valid target for this cancer, despite reporting its lower than normal telomerase levels. Don't know though, just guessing.

Thanks for that sentence : "As i understand it cell immortalisation occurs in a pre-cancerous state which helps the cell accumulate more mutations thereby becoming cancerous". You're right, and that makes it strange. How dit those cells become tranformed ? The usual view as you said is that cells need time and numerous duplications to accumulate enough mutations. They don't have that kind of time here.

After some research I found that thyroid medullary carcinomas can be (25% of cases) hereditary, due to the mutation of the RET genes.
In the others cases, RET mutations are found most of the time (perhaps alongside other mutations, they don't know yet).

In this case, maybe it can explain why immortalisation is not necessary. Those cells are transformed because of one or a limited number of mutations. Once they are transformed, even if they stop growing after 50 duplications, it's of no consequences.
Indeed, patient death occurs after 45 duplications at most (10^13 cancer cells).

Sounds feasible. The article also states how the p53 and pRb suppressors are under expressed in thyroid medullary carcinomas - i assume more so than in other cancers. Also it states:

Thus, these cells must have gained mechanisms to prevent the induction of senescence or apoptosis due to critically short telomeres.

Is the neoplasm burden less in thyroid cancers than in other cancers? Just wondering given the anatomic position of the thyroid around the throat might cause death with less mass than in other locations.

I didn't have a chance to read the article, but in regards to cell culture, cancer cells can act very differently in vivo versus in vitro. For example it is actually very difficult to excise cells from a tumor and get these cells to become immortalized in a petri dish. SV40 vectors and other "growth" inducing vectors often need to be transfected into a cancer cell in order to achieve an immortalized cell line.

Why the apparent difference between cultured cancer cells and these cells in a tumor. Well that really is the question that scientists are struggling to answer. It is increasingly apparent however that the ECM and other signaling cues in the body are vital for tumor progression.

Or in other words, think of a tumor as an organ. Evil organ that wants to kill you, but an organ nonetheless. Just like any other organ, take out one portion, it wont act the same in a petri dish than it does in the body.

Even though cancer cells are referred to as "immortal" (in the popular literature), they are not necessarily so. In fact, most are not. Cancer happens because cells start to divide faster than they should, so even if they eventually die, the body ends up having a tumour anyways.

Cheers