Subsets of cancer cells are known to reactivate telomerase and bypass senescence in many cases, but in order for a cancer to achieve lethality, is immortality of any cell subset actually necessary? Couldn't rapid and untimely cell division overwhelm the host body resulting in death before the cancer cells actually reach the Hayflick limit?
Also, since mice are known to have long telomeres compared to humans, could the potency of transformation of mouse cells by human oncogenes be magnified since they do not have to overcome telomere crisis as quickly? For example, if human cells are transduced with oncogene X, they may rapidly divide but produce a non-lethal cancer because the cells are just accelerated to telomere end crisis and die out. But if mouse cells are transduced with oncogene X, the cells may exhibit a greater number of total divisions before telomere end crisis occurs, allowing the population to expand to lethal proportions.
I ask this because many oncoproteins have no known mechanistic connection to telomeres or immortality, and many cancer models can achieve lethality just by the transformation of cells with a single oncogene.
This could also explain why so few patient cancers are able to be successfully developed into immortal cell lines.
I really doubt that a given cancer cell is immortal.
This is the extraordinary complexity of a given cancer (for example in terms of tumor microenvironment) that unfortunately makes a cancer a "long-living" tissue ...
An "immortal" cell line is composed of billion of cells if you take into account the number of passages...
I think that an "immortal" cancer cell line developing in a plastic flask has actually noting to do with a "true" cancer, as the ones that unfortunately develop in patients.
it is so unfortunate that about 90% of researchers indentifying new anticancer compounds from natural origin claim great successes and hopes in efficiently combating cancer ... because they succeeded in killing these poor orphan cancer cells that are prisonners in platic flasks ...
I suggest to have a look on the attached articles.
I am currious to know whether you will have the same thoughts about the "immortality" of a given cancer cell after having read these articles.
Best regards
Robert
Thank you for the response and links. I have modified my question as I felt it was unclear based on how you responded.
Hi Andrew,
You bring up some interesting points. However, a majority of cancers do maintain their telomere length in order to have limitless replicative potential, either by expressing telomerase (~80-90%) or by alternative lengthening of telomeres (ALT). The answer may lie in the phrase limitless replicative potential...potential not true immortality. Those cancers that do not maintain telomere length, such as a subset of neuroblastomas, will spontaneous regress. There may be many other factors in play when it comes to making immortalized cell lines, like understanding microenvironment and culture conditions.
Hi,
There is growing evidence that not all cancers are immortal, especially in the early stages of progression. Ron DePinho's group and others including us have published evidence for telomeric crisis occurring within early cancers. The lifespan limits of human cells can allow a non-immortal clone to get pretty big if it has evaded primary senescence but is not yet maintaining its telomeres yet, so it is not really surprising if immortalization might sometimes be a late event in progression. We explanted a lot of early primary melanoma samples and found that actually the majority were not immortal.
See: Soo JK, et al.Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression. Pigment Cell Melanoma Res 24:490-503, 2011. (Available on my ResearchGate page, where there is also a recent review on this.)
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