Tunneling Nanotubes Evoke Pericyte/Endothelial Communication during Normal and Tumoral Angiogenesis

There are many kinds of cancers in the world, and many people are suffering by them. Gliobastoma (GBM) is a kind of the brain cancer, which is typically classified as an astrocytoma. Astrocytoma is caused by cancerous astrocytes, which play an important to support endothelial cell to form blood-brain-barrier. GMB is a deadly cancer, patients’ life expectancy is only 14 months with treatment, the senator John McCain is also suffered by this cancer and passed away. Personally, I believe cancer treatment is important for human being. This paper has an interesting idea that cut the communication between tumor cell and normal cell but not just remove the tumor, this way probably can be more helpful in prevent metastasis than remove tumor.

Tunneling nanotubes (TNTs) are cellular structures use for connect two cells that have been described in recent years. TNTs is often though to connect blood vessels or blood vessel formation, and pericytes are cells that found around blood vessels – specifically capillaries. Pericytes and TNTs may be involved in blood vessel formation, cellular communication transfer of organelles between cells. This study is trying to find the connection between pericytes and TNTs in the brain by examining these connection in normal fetal brain specimens and the primary tumors specimens of glioblastoma which both are growing brain tissue and would require cell-to-cell communication and angiogenesis. The goal is to determine targeting TNTs, it could be a way to treat brain cancer by attacking the pericytes and stop TNTs form growing.

This study use the immunostaining and immunofluorescence confocal microscopy to the specimens. This is types of microscopy that enables scientists to examine individual cells and cellular molecules in detail. The scientists use 6 autopsy specimens of fetal brain that were collected form fetuses at 18 and 22 weeks of gestation, which is the period of TNTs development the human brain region, telencephalon. They also examined other 6 glioblastoma samples which were collected form primary tumors specimens obtained in previous study. All the samples were dissected into 20μm in thickness and been stained by specific solutions and antibodies to label cell specific protein. They used eleven primary antibodies and 9 secondary antibodies for the labeling, and use laser confocal microscopy to analysis and measurements.

The result of labeling indicated that two protein called CD146 and NG2 can be used for identifying pericyte TNTs. Based on these results, the studies of fetal tissues use the developing human telencephalon with double immunostainings to see how  show that pericyte derived TNT were involved in vessel growth and sprouting. This experiment shows that the endothelial tip cells (ETCs) and EC are not involved to the TNT formation, and also confirm that NG2 and CD146 can used for labeling pericyte-like cells and on their short TNTs.

 

 The source of the image

Because one of the histopathological features of GBM involves the aggressive proliferation of blood vessels and pericytes, the researcher also looked for evidence that similar pericyte TNTs are involved. This study revealed that these tumoral areas do have rich network of TNTs, just like the developing cortex of human fetuses.

The study also used the pericytes which were grown in culture on a matrix called Matrigel to confirm that ability of isolated human brain vascular pericytes can indeed reproduce such structure in vitro. Therefore the study use three different ways connect pericytes derived TNTs to blood vessel formation.

The conclusions show that brain pericytes have a role of an origin for TNTs in the brain, and may be involved in earliest phase during normal and pathological angiogenesis. However, this study only shows the relation between pericytes and TNTs, they still don’t know how it relate to larger structure, and they also don’t know how they form and their function, but it still a start. Pericyte TNTs in glioblastoma may open out a possible TNT-based communication between vessel cell components and a target to treat GBM in the future.

 

References:

The original article 

Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis.

Errede M, Mangieri D, Longo G, Girolamo F, de Trizio I, Vimercati A, Serio G, Frei K, Perris R, Virgintino D.

Fluids Barriers CNS. 2018 Oct 5;15(1):28. doi: 10.1186/s12987-018-0114-5.