This paper suggests that the Brazilian wasp venom targets cancer cells and makes holes in the membrane large enough for the important cell reproducing things, like RNA, to spill out making the cancerous cell unable to reproduce and otherwise worthless until it gets disposed of regularly. It also apparently leaves normal cells alone (or has limited/no effect on them).
Edit: It does this in a petri dish, not a living body.
There is a strong upregulation of the Mevalonate Pathway in a lot of cancer cell lines. This is at least partially explained by hyperactivation of TORC1 (Controls cell growth and proliferation) signaling through its function of cleaving SREBPs (Sterol regulatory element binding proteins which positively regulate sterol synthesis). SREBP activation will result in increased increased transcription of genes involved in sterol and fatty acid synthesis such as those found in the Mevalonate Pathway.
It isn't so much that they are transported in a regulated and unique fashion to the outer cell membrane as much as they utilize the existing machinery to reach the cell membrane. Because the pathways that regulate their synthesis are hugely upregulated, there are more sterols and fatty acids.
Intelligent people tend to overlook that stuff. I've said dumb things to doctors that would typically illicit a laugh, but they just kind of look at me and continue on like nothing happened.
It's more likely busy people overlook that stuff. I know a plenty of bored intelligent people that love correcting vocabulary grammar and pronunciation.
Would you happen to know if anyone has used the upregulation of fermentation (Warburg effect) as a way of targeting cancer cells for treatment recently? It seems like the research was limited only to the mid-2000s.
I think both. There are lots of pre-clinical things going on, as well as some trials and lots of retrospective studies (did people who took metformin in the past get less cancer?)
I really only know that that effect exists. I don't know much beyond that. I just assumed it was a result of an overgrowth of cells preventing easy access to oxygen from the blood supply. No oxygen means no respiration which means cells need another method to generate ATP. Fermentation is the easiest answer. At least that was my assumption.
Edit: I could see a knockdown of VEGF (Vascular Epidermal Growth Factor which promotes blood vessel growth) or HIF1-a (hypoxia inducible factor which is a major stress response pathway which responds to low oxygen and regulates VEGF) resulting in a starvation of those cells that are lacking nutrients and oxygen and primarily utilizing fermentation, but I think especially with HIF1-a there would be huge off target effects and it would result in a mass of necrotic tissue that would need to be surgically removed. The above is entirely speculation though so I'll see if there are any good papers on this stuff.
Edit 2: a quick check on Wikipedia says my original assumption was wrong about what exactly the effect is. It seems like it is a secondary effect though to other mutations.
Your cell synthesizes the outer lipid bilayer of your cell. They exist in all cells and are produced by processes inside of the cell. In cancer cells you know that they are reproducing and making things in a wacky way. It's possible that the cancer cells mechanisms for producing a "rare" type of lipid is jacked up such that there is a higher amount in the cancer cell membrane vs normal cells
OK but cancer as a disease is diverse depending on the mutations made to obtain unregulated growth and immortality. I would guess that this rare type of lipid wouldn't be consistent between different cancer types. Is there a specific cancer that produces a high lipid content in its membrane that this would effect more than a regular cell?
One thing you might be interested in looking into is the relationship between PI lipids and cell signaling. It is known that cell signaling is altered in cancer cells so potentially PI might play a role. I don't know about specific cell lines though.
Cool thanks for the suggestion. I am actually taking a signal transduction class this semester in my grad program and we are covering that in about a month. This has me curious so I am checking it out now.
I'm assuming it has to do with making it harder for the immune system to recognize it as a non-self/cancerous cell.
In healthy cell membranes, phospholipids called phosphatidylserine (PS) and phosphatidylethanolamine (PE) are located in the inner membrane leaflet facing the inside of the cell. But in cancer cells, PS and PE are embedded in the outer membrane leaflet facing the cell surroundings.
Although, I'm just speculating. Don't take my word for it 100%.
No, but all cancer cells do have an abnormal amount of fat molecules on the surface. If this treatment were ever successful, I would imagine it as step 1 in the process to a cancer purge (it would weaken the cancer cells for something else that could easily eliminate exposed cells).
I'm not sure on the full implications of this research, but it would be either what you said, or that this would be stage 1 therapy to break open the cancer cells for a following treatment that would destroy them.
Yes they are completely different things, but both aim to kill fast dividing cells.
The fastest dividing cells are most vulnerable, and those are the tumor cells (and some healthy cells also, such as hair follicular cells) .
Unfortunately tumor cells are also faster to evolve mechanisms to withstand these effects than normal cells, so it's always a balancing act between giving enough dose to kill the tumor cells and not kill everything else too, and not giving a too low dose to allow the tumor to evolve escape machanisms.
In healthy cell membranes, phospholipids called phosphatidylserine (PS) and phosphatidylethanolamine (PE) are located in the inner membrane leaflet facing the inside of the cell. But in cancer cells, PS and PE are embedded in the outer membrane leaflet facing the cell surroundings.
Basically, there are some little bits and pieces in all of your cells. In healthy cells, these particular substances are hidden safely away where the venom can't touch them. In cancerous cells, everything is all messed up and these substances are on the outside where they can be touched.
To normal cells, the venom doesn't do anything. Without PS and PE, the venom can't really react with them.
However, when the venom touches PS and PE, it (basically) rips it right out of the cell. Because PS/PE are an important part of the cell wall, ripping them out basically rips a big ol' hole in the cell wall which causes the cell to collapse.
To put this in super simple terms, the venom reacts with a substance present in the cells. In cancerous cells, these substances are on the outside. On normal cells, these substances are on the inside where they can't be touched.
At the very least, that's presently the speculation by the scientists.
ELI5: Kool-Aid man can't go through brick walls and that's how normal cells are made. Cancerous cells are a little messed up so there's a lot of mortar on the exterior and Kool-Aid man goes through them like they're paper.
Does the venom require both PS and PE together or does either one work? I learnt (admittedly a long time ago) that PS was flipped to the surface of normal cells as part of apoptosis. If so how do cancerous cells avoid this mechanism?
You're right, but this may not be a problem as apoptic cells are bound to die anyway.
On the other hand, some immune cells also have PS on theír surface during activation, which could pose a bigger problem if you kill off those
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Edit: resistance to apoptosis is one of the major mechanism of tumorigenesis. tumor cells do this by, e.g. downregulation cell death inducing receptors, ignoring cell death inducing signals or just plainly refuse to die
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u/[deleted] Sep 01 '15
Who wants to ELINAS this for us?
(Explain like I'm not a scientist)