Do hypoxic or necrotic cells release chemicals that inhibate the proliferation of the surroundings cells ?
And do you think that such chemicals could alone stop a multicellular spheroid from growing ?
Meaning I could understand a spheroid stops growing because that there are not anymore anough nutrients in the media, or because there is a flow of proliferating cells towards the center do to the fact that cells are dying there. But could the inhibition due to chemicals be a cause of the cells stopping to grow ?
(I'm asking that cause of some experiments I'm observing)
Hi Joesph,
I don’t think I’ve come across any literature that suggests that hypoxic cells will inhibit the growth of another non-hypoxic cell. I do, however, believe that cells in the interior of the spheroid (i.e., quiescent and hypoxic) know that the nutrient supply is low. Hence, quiescent cells undergoing growth arrest to ensure that they survive. On the other hand, there are cells that evade quiescence, and continue to proliferate. I believe that when this happens within a tumor (or spheroid), those cells are the ones that suffer from hypoxia. Moreover, unless they (i.e. hypoxic cells) escape the tumor (or spheroid), they will eventually die—hence the emergence of a necrotic layer.
As for your second question, what are your culture conditions? You mentioned chemicals inhibiting growth, are you adding any chemicals that may influence proliferation? If not, and assuming this is an in vitro study, then there could be a few factors that could be influencing spheroid growth. The first is the type of culture dish are you growing your spheroids in. The surface area and loading capacity of the dish affects spheroid growth. So therefore, just because the size of the spheroid is not increasing, does not mean that there aren’t proliferating cells present. I know this to be true because I have passaged spheroids to produce secondary and even tertiary spheroids.
Have you done any testing to determine the state of the cells within the spheroids? That is, what stage in the cell cycle they are in. You could dissociate a few of them and use flow cytometry to check the cell cycle. It’ll give you an idea of whether or not proliferation has ceased. Or you could passage them, and if secondary spheroids form, then at least you know that viable cells present and that proliferation is happening.
I hope this helps.
Thank you ! This is very clear.
In the experience, there are just tumor cells and solvant in ultra-low binding plates. There are no other chemicals.
The thing that makes me think there might be an inhibition is because most of the spheroids start with a few cells, but stop growing quite quickly, at a radius where it's unlikely there is a necrotic core. So I was thinking maybe the hypoxic or quiescent or the few necroting cells release some molecules that inhibate the growth of the surrounding cells. According to what you're saying, maybe not only the quiescent cells stop their cycle, but they are also signaling a lack of nutrients and those signals make the other cells stop their cycle too.
There has been no testing yet. We should do some soon.
Have a nice week-end
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