Reply appreciated. Thank you for giving me a bit to stew on. I remember reading about early fights in favor of oncogenes as the source of cancer. In a way, this is cancer research come full circle back to non-genetic sources of tumors. Think exosome-budding-protein could be the next big cancer blocking target?
Thanks. I have my doubts that it'll be a protein, but who knows. Prions are crazy. Maybe exosomes can carry something like that. There was a recent paper showing that exosomes are enriched in transcription factors. I suppose there could be a protein linchpin in there. From my experience, there are a number of avenues to tumor, and a number of ways to potentiate each path. For some tumors, if you find an early catalyst, you are all set. But, for some like glioblastoma, there are a number of paths to a similar malignancy, and any treatment will only hit a subset. What's worse, is that they are so unstable, they can become independent of the pathway that underpinned their malignancy. Unfortunately, for those tumors, the closer you get to a treatment that includes them all, the more likely you are to have something systemically deleterious. I have the half-baked notion that exosomes could be an appropriated viral mechanism from long ago, not unlike mitochondria. But, it really doesn't matter the origins; viruses demonstrate an efficient way to broadcast a genetic message, there's no reason why cells couldn't convergently evolve onto similar behavior. What I am saying, is that perhaps the body 'infects itself' all the time as a matter of course. It would be an interesting way to keep such a large system in sync. This 'infection' machinery going awry might be an overlooked component of cancer. Of course, this might not be the case, or maybe it's only true in some contexts, but IMHO it's worth thinking on. We draw distinctions between cells/tissues/organs/etc. But a nucleotide has no idea what it is part of, or how it is put to use. Do miRNAs serve cells, or tissues, or organs? It will serve any of them to the extent that it performs a useful function, and thus, is probably serving them all. For my part, I am currently looking into if something makes a cell 'listen' to the miRNAs in exosomes, or alternately, if they might be inclined to 'ignore' them. I have a candidate, and I have the miRNA transfer model that we previously used.
Yeah, I was talking to a proteomics guy about variance in protein activity across a tumor. He was saying that if you took samples from far apart on a tumor, you saw almost no correlation in activity. In fact, if you took samples from right next to each other on a tumor, you saw almost no correlation in activity. Cancer's weird, miRNAs are weird, and now I'm going to throw "exosomes" are weird into that bucket, too. Still, food for thought in all of the above.But, for some like glioblastoma, there are a number of paths to a similar malignancy, and any treatment will only hit a subset.