Cytocapsular tubes

“Extraordinary claims require extraordinary evidence”  Carl Sagan.  That goes in spades for a recent PNAS article vol. 115 pp. E1137 – E1146 2018 —

Start by looking at the following 3 videos




Unfortunately, to get to them, it appears that you must be a PNAS subscriber, so I’ll tell you what they show.

First, some background. Cell culture usually involves putting them into a Petri dish, something inherently two dimensional, but most cells in our body live in a 3 dimensional environment. So this work implanted Human Mammary Epithelial Cells (HMECs) into a 3 dimensional matrix of Matrigel (an extracellular matrix surrogate secreted by mouse sarcoma cells, containing, laminin, nidogen, collagen and heparan sulfate proteoglycans) Matrigel also contains the growth factors Transforming Growth Factor Beta (TGFbeta) and Epidermal Growth Factor (EGF), both of which prevent differentiation and promote proliferation. The 3d Matrigel matrix is softer and spongier than the hard surface of a Petri dish.

The behavior of these cells in the Matrigel is completely different than that usually seen. In fact no one has ever seen anything like it before, which is why, if possible you must look at the 3 movies the paper supplies in the supplementary material (referenced above).

The cells move around, but nowhere to be seen are the lamellipodia or the filopodia seen in 2 dimensional cell culture.

In the first movie a small cell repeatedly generates and retracts multiple membranous protrusions called cytocapsues (some larger than the cell itself) which the cell sometimes enters.

The second has multiple cells within the tubes formed by the cytocapsules (cytocapsular tubes) migrating within them. The cells drag the tubes through the matrix, without breaking the tube or allowing another tube to merge with it.

If replicated, this work has bearing on embryology, normal organ function and cancer metastasis.

No one has ever seen anything like this. Why not? The authors say that ‘only when the polymerization, density and viscoelasticity of the Matrigel is tightly controlled are the tubes seen. Unlike secreted extracellular vesicles, cells get inside the cytocapsular tubes. The tubes themselves interconnect and form networks. The tubes degrade and decompose without cells inside them.

They note that polymerized actin (microfilaments) are present under the tube membranes.

Even though the membranes are mostly lipids, proteins are required, and eIF4E levels are elevated. Inhibiting it suppresses cytocapsular tube generation.

It’s worth repeating Sagan – “Extraordinary claims require extraordinary evidence” Stay tuned

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