Monday, August 21, 2017

Toward solving the stromal microenvironment puzzle!

(Image above showing the components of tumor stroma from this ResearchGate-hosted article)

A cancer cell alone in the body generally isn't a big deal. Maybe it starts dividing uncontrollably, but cancer cells can also starve. In fact, they generate more waste and use more energy than normal cells (textbook generalization) so, in a way, they're more vulnerable to needing support than normal cells. In order to form a tumor, that cell needs support from noncancerous cells to provide blood flow and structural support. We typically call all that other stuff stroma.

This new study in Science signaling reveals a ton of new information on what is going on in the stroma by using patient derived xenografts and reporter ion based quantitative proteomics!

Figuring out what is cancer cell and what is stroma can be tough -- however, in this system the cancer cells are human and the stroma cells are mouse! Much easier to sort out what is the stromal support response.

They quantify around 5,000 human proteins and close to 2,000 mouse proteins in these xenografts and -- all the sudden, patterns start emerging in the mouse protein response! This provides a better picture than we had before of what changes are occurring in the "normal" cells to support tumor progression.

During one of my postdocs I did a lot of data processing and QC on transcriptomes of cancer cells through xenograft tumor progression. While this database is undoubtedly useful, there are considerable challenges with microarrays when trying to determine what readings are from human and which are from mice. When you've only got 4 nucleotides, a lot that appears very conserved -- is more like...kinda conserved... 26 amino acids is a much more sensitive readout for determining protein-species assignment!

BTW, this new study used some great study design in advance of this project and the LC-MS workload was divided between an Orbitrap Elite and Q Exactive system.

No comments:

Post a Comment