Nav: Home

Blood biopsy: New technique enables detailed genetic analysis of cancer cells

May 15, 2019

ANN ARBOR--A new way to cleanly separate out cancer cells from a blood sample enables comprehensive genetic profiling of the cancer cells, which could help doctors target tumors and monitor treatments more effectively.

It is a dramatic improvement over current approaches because it also encompasses the variation among cancer cells within a single patient.

"This could be a whole different ball game," said Max Wicha, the Madeline and Sidney Forbes Professor of Oncology at the University of Michigan and senior physician on the study in Nature Communications.

Earlier techniques meant a trade-off between a comprehensive genetic profile of a limited subset of cancer cells, or capturing most of the cancer cells and only being able to look for a few genes. As a result, the genetic profiles often neglected important populations of cancer cells--including cells believed to spread cancer in the body.

"Our chip allows us to capture pure circulating tumor cells and then extract genetic information without any contamination from red and white blood cells," said Euisik Yoon, U-M professor of electrical engineering and computer science and senior author on the study.

Many modern cancer drugs work by going after cells with certain genes in play--genes that flag their identities as cancer cells. But these genes aren't uniformly active in a patient's cancer cell population and can change over the course of treatment.

Repeated biopsies to monitor the tumor are painful and potentially dangerous for the patient. Capturing cancer cells from blood samples offers a noninvasive way to observe whether the cancer is disappearing or whether it is becoming resistant to the treatment.

"It allows you not only to select targeted therapies, but to monitor the effects of these therapies in patients by doing this blood test," Wicha said.

Using this method, the team collected and analyzed 666 cancer cells from the blood of 21 breast cancer patients.

The genetic analysis confirmed that even within a single patient, the cancer cells often behave very differently. Wicha's group has previously shown that cancer metastasis is mediated by cancer cells that have the properties of stem cells. Although cancer stem cells make up only a few percent of a tumor's cells, they make up a higher proportion of the cancer cells in the bloodstream. In this study, about 30-50% of the cancer cells captured from the blood samples displayed stem-like properties.

This population is particularly easy to miss with techniques that capture clean-but-incomplete samples of cancer cells from patient blood by grabbing onto proteins on the cells' surfaces. Stem-like cells are on a spectrum between two more-typical cell types, which means that they don't display consistent protein markers.

To get a clean and unbiased set of cancer cells from a vial of blood, the team started with a technique that removes blood cells by sorting the blood sample according to cell size. Starting with about one cancer cell in a billion blood cells, this step left only about 95 or so blood cells for every cancer cell. But that's still far too contaminated for a detailed genetic analysis.

The new method, which the researchers call Hydro-Seq, gets rid of those last blood cells and then analyzes each cell.

The key technology is a chip with a system of channels and chambers. It traps cancer cells one at a time by drawing fluid through a drain in each chamber, which gets plugged when a cancer cell arrives. Once the chamber is plugged, cells in the channel pass it by and get sucked into the next chamber. Then, to "wash" the blood cells off the chip, they ran clean fluid backward through the chip and drew it out again, taking nearly all the rest of the contaminating cells along.

With a clean sample of isolated cancer cells, the team did the genetic profiles. They went after the cells' "transcriptomes"--basically, snapshots of what DNA was being read and used by each cell. This revealed the cells' active genes.

They captured the transcriptomes with barcoded beads, a method that until now was difficult to use with small cell samples. The team dropped a barcoded bead into each chamber and then closed the chambers before destroying the cell membranes. This released the RNA--the little bits of genetic code recently read from the cell's DNA--so that the RNA attached to barcoded genetic code on the bead. The team could then analyze the contents of each cell separately.

"Before, we could measure two or three genes at a time with staining methods, but now we get a comprehensive picture of circulating tumor cells by measuring thousands of genes in each cell at once," said Yu-Chih Chen, U-M assistant research scientist in electrical engineering and computer science and co-first author on the study.

Cancer treatment can be a moving target, with cancers changing their gene expression as drugs kill off some cells but not others. Monika Burness, U-M assistant professor of internal medicine at and co-author on the study, expects to be using the new device to track the progress of patients in an upcoming drug trial.

"It's a very powerful tool to monitor--at the cellular level--what a treatment does to tumors over time," said Burness, who studies new drug therapies for cancer patients.
-end-
The study is published open-access in Nature Communications.

Wicha is also director of the Forbes Institute for Cancer Discovery. Yoon is also a professor of biomedical engineering. Chen is also an emerging scholar at the Forbes Institute for Cancer Discovery.

This work was funded by the National Institutes of Health, Breast Cancer Research Foundation, Forbes Institute for Cancer Discovery and U-M Coulter Translational Research Partnership Program. The devices were made at the U-M Lurie Nanofabrication Facility.

Study: https://www.nature.com/articles/s41467-019-10122-2.epdf?author_access_token=IF7MeCNHqtM1eI0oskHccNRgN0jAjWel9jnR3ZoTv0Mcwdo80HMGAlvpKgnT9SG0yN8waqB8fFueSYQ8zU7tr4saqyhwkneOY4YVECJy1tGNB5XNVupx5IZBszbxcCOYc2WLbbNdGz6JD7cSGJFXmw%3D%3D

Yoon Lab: http://yoon.eecs.umich.edu/

Wicha Lab: http://www.med.umich.edu/wicha-lab/

Burness Lab: https://burness.lab.medicine.umich.edu/

University of Michigan

Related Stem Cells Articles:

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
TSRI researchers identify gene responsible for mesenchymal stem cells' stem-ness'
Researchers at The Scripps Research Institute recently published a study in the journal Cell Death and Differentiation identifying factors crucial to mesenchymal stem cell differentiation, providing insight into how these cells should be studied for clinical purposes.
Stem cells in intestinal lining may shed light on behavior of cancer cells
The lining of the intestines -- the epithelium -- does more than absorb nutrients from your lunch.
More Stem Cells News and Stem Cells Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.