In cancer cell culture, the growth factor component of FBS seems particularly unnecessary, given that cancer is a post-natal disease and cancer cells are defined by cell autonomous growth factor signaling. Yet, FBS is required for rapid cancer cell proliferation. Why? Oliver went to find out. - ThreadSky

lucasbsullivan.bsky.social • 5 days ago

In cancer cell culture, the growth factor component of FBS seems particularly unnecessary, given that cancer is a post-natal disease and cancer cells are defined by cell autonomous growth factor signaling. Yet, FBS is required for rapid cancer cell proliferation. Why? Oliver went to find out.

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lucasbsullivan.bsky.social•5 days ago

Using live cell imaging of cancer cell proliferation in reduced serum conditions, Oliver found that cell proliferation doesn’t immediately slow, it decays over time, suggesting the consumption and depletion of essential nutrients.

lucasbsullivan.bsky.social•5 days ago

Indeed, testing various additives, he found that this “depletion phenotype” was largely driven by the need for metals and lipids, both absent from most basal media formulations. However - serum provides a multitude of potential lipid species to uptake – which lipids are actually consumed by cells?

lucasbsullivan.bsky.social•5 days ago

Quantitative lipidomics from media gave a clear answer – albumin-associated lipids (fatty acids, LPCs, LPEs). Importantly, supplementing cells with an ITS additive (containing missing metals) and any of these albumin-associated lipids equivalently supported serum-free cancer cell proliferation.

lucasbsullivan.bsky.social•5 days ago

Oliver went on to use this defined system, free from FBS confounding the lipid environment, to characterize albumin-associated lipid uptake kinetics (mass action driven) and to determine that lipid scavenging is a necessary lipid acquisition route for many cancer cells.

lucasbsullivan.bsky.social•5 days ago

Recent research has clearly shown that the metabolic environment is a major determinant of cell function. Our hope is that this work will provide opportunities to compare serum-free conditions with physiological contexts to better understand the nutritive functions of the physiological milieu.

lucasbsullivan.bsky.social•5 days ago

This work also supports a crucial role for lipid scavenging, which we believe is an underappreciated requirement for cancer cell metabolism. We also think that the description of FA uptake as primarily concentration driven helps contextualize well described effects of specific FAs on lipotoxicity.

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