Last week, my first paper got rejected, so I guess I might as well publish it myself here 🙂
What we are trying to do is to see whether or not extracellular vesicles are useful as cancer biomarker in liquid biopsies. Liquid biopsies are currently clinically applied to supplement diagnostic tools such as PET/CT or MRI in the management of metastatic cancer patients. It typically entails taking a blood sample (several ml) and screening it for presence of circulating tumor cells (CTCs), which are implicated in disease progression and whose concentration correlates with survival probability. In other words, by studying a few ml of blood, it can be established whether the condition of the patient is improving or not and based on the results, the treatment plan can be modified.
A big advantage over the mentioned imaging systems, besides the cost, is the frequency at which it can be performed; given the harm inflicted on the patient by e.g. the contrasting agents, those scans are usually performed only several times per year.
A big disadvantage is the scarcity of CTCs. There usually are just a few CTCs present in a ml of blood, compared to a billion red blood cells. So, elaborate enrichment steps are required and experienced operators are necessary to tell CTCs apart from other cells. My project aims to solve that issue by focusing on extracellular vesicles (EVs). These sub-micron bioparticles are excreted by most cell types and found in all body fluids. They are among other things involved in intercellular communication and carry (membrane) protein as well as nucleic acids. EVs are much more abundant; there are several trillions of EVs in one ml of blood. The “signal-to-noise” ratio of tumor-derived EVs (tdEVs) to other blood components is also much more favorable; their concentration is elevated in cancer patients.
That leaves us with two challenges:
1) How do we isolate tdEVs from blood samples?
This requires highly specific recognizing elements and the major challenge here is to reduce the non-specific interaction of the system with other blood components. Blood is an extremely heterogeneous, complex medium full of all kinds of particles that, depending on the characterization method, very closely resemble tdEVs. Without elaborate control experiments, it is very easy to mistake a “false positive” for an EV and to draw conclusions based on signals emanating from contaminants. In the relatively nascent field of EV research, this still frequently occurs and a consensus of what exactly constitutes an EV is lacking.
2) How do we quantify them?
Biologists, put blunty, like to use microscopes to get an idea of what is going on. However, due to their size, EVs are typically not picked up by optical instruments. Less than one percent of EVs is larger than 1 micrometer, so equipment that is used to image cells (in the order of 10 um, i.e. having a volume a million times larger than the average EV) is just not sensitive enough to detect single EVs.
We came up with successful solutions to these problems, aided by surface modification of a non-typical material, but on second thought, let’s wait until it does get published until I throw anything about it online, free for everyone to scoop 🙂
Until next time!