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I am not an oncologist but I thought that metastasis was more related to a tumor growing too close to a major blood highway. If some of those cells that like to

by zer8k 3y ago

I am not an oncologist but I thought that metastasis was more related to a tumor growing too close to a major blood highway. If some of those cells that like to grow out of control get into that system they end up getting lodged all over the place. It seems less like "enabling and executing" and more like it just grows and grows until it leaks out. The ability for tumor cells to suppress the immune system however is fascinating. It's almost like an alien.

vibrio 3y ago
Cancers actually drive blood vessel growth into the tumors to feed themselves. I’m sure they leverage that as part of dissemination. Different primary tumors (eg Prostate, breast, lung) have preferred sets of metastasis sites that are not always explained by where they get stuck due to getting into the blood supply. Even getting into the blood supply requires functions of degrading extra cellular matrix, evading immune surveillance, getting out of blood vessels and “setting up camp” at the news destination, and those requirements can be cancer and/or met site preferential. Much of the immune suppression mechanisms are actually regulated systems normal cells use to prevent runaway inflammation. Cancer finds that function and highjacks it to “hide”. Conversely (to further illustrate complexity), some cancers use aspects inflammation as ”fuel” to drive tumor growth especially early in the cancer. I do agree- it is all truly fascinating.with that said: Fu*k cancer.
- matthewdgreen 3y ago
  What I’ve never understood is how all this complex cooperative behavior emerges out of a relatively small number of mutations. I get that these are all repurposing of existing mechanisms, but still the overall coordination seems so much more purposeful than something that would happen with a few initial mutations and then some further selection. Particularly things like metastasis, which sounds like a many-stage process that would be hard to spontaneously evolve.
  - Teever 3y ago
    Yeah, it kind of makes you think that maybe some sort of cancer blob is the default state of cells and that everything that goes into making a collection of cells into a particular species is what's holding cancer back.
  - BHSPitMonkey 3y ago
    > but still the overall coordination seems so much more purposeful than something that would happen with a few initial mutations and then some further selection. Isn't this just selection bias on a grand scale? You're looking at a specimen where the parts happened to end up arranged in a way that allows it to exhibit these properties that seem like coordination, while not paying much attention to the quintillions of specimens that did not.
  - vibrio 3y ago
    It is more than just a few mutations. A good number of the common earlyish driver mutations are in the systems that detect and repair damage to DNA, which then accelerates mutation accumulation. (At some cost to stability of that lineage, but overall there are obliviously formulas that work) And I’d also point out that these functions that are “sought after” by cancer are not all de novo, some things are complex functions that encoded for use by other normal cells at a other times and places in development of the organism. Some key mutations that enable the use of those functions by the cancer are crucial moments cancer development. Also many key mutations are loss of functions, which are often easier to accumulate. A example of genetic Losses of function is losing “contact inhibition” where normal cells stop growing when they get neighbors. Cancer cells loose this inhibition and just continue growing. This alone would require a suite of mutations. Another comment in the thread talks about cancer evolution and the good of the organism not making sense. Cancer doesn’t care about the organism. The organism has evolved many layers of checks and balances that can work for decades, but throw in time and poisons like smoking, UV damage, and there will be loopholes found. Cancer is persistent and has the entire genome of functions to turn on and off in various ways. Seriously Fu*k cancer.
  - ssener2001 3y ago
    Human body and immune cells and cancer cells all are complex. It is clear that for blind force , unconscious nature, and aimless chance could in no way interfere in such percipient, delicate art, and conscious subtle wisdom, and perfect providential balance; they could not be their work. It is impossible. It is also utterly impossible that living creatures made themselves for then each of their particles would have to possess comprehensive knowledge and wisdom like a god, to be able to know , see and make all the parts of their bodies and form it , indeed , it would have to know ,see , and make everything in the world connected to it. "Whoever created the mosquito's eye ,created the sun. Whoever ordered the flea' stomach, ordered the solar system." from Quran's light
blacksmith_tb 3y ago
Many metastases spread through the lymphatic system, so more like the circulatory 'back roads' you might say.

by zer8k 3y ago

vibrio 3y ago

Cancers actually drive blood vessel growth into the tumors to feed themselves. I’m sure they leverage that as part of dissemination. Different primary tumors (eg Prostate, breast, lung) have preferred sets of metastasis sites that are not always explained by where they get stuck due to getting into the blood supply. Even getting into the blood supply requires functions of degrading extra cellular matrix, evading immune surveillance, getting out of blood vessels and “setting up camp” at the news destination, and those requirements can be cancer and/or met site preferential. Much of the immune suppression mechanisms are actually regulated systems normal cells use to prevent runaway inflammation. Cancer finds that function and highjacks it to “hide”. Conversely (to further illustrate complexity), some cancers use aspects inflammation as ”fuel” to drive tumor growth especially early in the cancer. I do agree- it is all truly fascinating.with that said: Fu*k cancer.

matthewdgreen 3y ago
What I’ve never understood is how all this complex cooperative behavior emerges out of a relatively small number of mutations. I get that these are all repurposing of existing mechanisms, but still the overall coordination seems so much more purposeful than something that would happen with a few initial mutations and then some further selection. Particularly things like metastasis, which sounds like a many-stage process that would be hard to spontaneously evolve.
- Teever 3y ago
  Yeah, it kind of makes you think that maybe some sort of cancer blob is the default state of cells and that everything that goes into making a collection of cells into a particular species is what's holding cancer back.
- BHSPitMonkey 3y ago
  > but still the overall coordination seems so much more purposeful than something that would happen with a few initial mutations and then some further selection. Isn't this just selection bias on a grand scale? You're looking at a specimen where the parts happened to end up arranged in a way that allows it to exhibit these properties that seem like coordination, while not paying much attention to the quintillions of specimens that did not.
- vibrio 3y ago
  It is more than just a few mutations. A good number of the common earlyish driver mutations are in the systems that detect and repair damage to DNA, which then accelerates mutation accumulation. (At some cost to stability of that lineage, but overall there are obliviously formulas that work) And I’d also point out that these functions that are “sought after” by cancer are not all de novo, some things are complex functions that encoded for use by other normal cells at a other times and places in development of the organism. Some key mutations that enable the use of those functions by the cancer are crucial moments cancer development. Also many key mutations are loss of functions, which are often easier to accumulate. A example of genetic Losses of function is losing “contact inhibition” where normal cells stop growing when they get neighbors. Cancer cells loose this inhibition and just continue growing. This alone would require a suite of mutations. Another comment in the thread talks about cancer evolution and the good of the organism not making sense. Cancer doesn’t care about the organism. The organism has evolved many layers of checks and balances that can work for decades, but throw in time and poisons like smoking, UV damage, and there will be loopholes found. Cancer is persistent and has the entire genome of functions to turn on and off in various ways. Seriously Fu*k cancer.
- ssener2001 3y ago
  Human body and immune cells and cancer cells all are complex. It is clear that for blind force , unconscious nature, and aimless chance could in no way interfere in such percipient, delicate art, and conscious subtle wisdom, and perfect providential balance; they could not be their work. It is impossible. It is also utterly impossible that living creatures made themselves for then each of their particles would have to possess comprehensive knowledge and wisdom like a god, to be able to know , see and make all the parts of their bodies and form it , indeed , it would have to know ,see , and make everything in the world connected to it. "Whoever created the mosquito's eye ,created the sun. Whoever ordered the flea' stomach, ordered the solar system." from Quran's light

blacksmith_tb 3y ago

Many metastases spread through the lymphatic system, so more like the circulatory 'back roads' you might say.