Patient cancer cells reliably grow on new 3D scaffold, showing promise for precision medicine

October 02, 2019

ANN ARBOR--A new 3D structure for growing cell cultures could enable doctors to test medications on model tumors grown from a patient's own cells, according to results from a team of engineers and cancer researchers at the University of Michigan.

Unlike previous devices, the new structure is made from protein fibers that cells know how to modify.

"We can potentially use the cultures to do things like drug testing or single cell analysis, which may help us identify the best treatments for a patient's cancer," said Gary Luker, U-M professor of radiology.

At present, some patients have samples of their cancer cells grown in mice for drug testing and analysis, but the cancer cells don't always grow and the process takes months, Luker said.

An advanced petri dish, known as a 3D scaffold, could enable doctors to get answers about the effectiveness of drugs in days or weeks. But earlier scaffolds, trying to mimic the structure and composition of the gel-like network that binds a collection of cells into a tissue, also have mixed records.

"Rather than trying to guess at what the tumor cells' microenvironment ought to be, we've made a space where they can create their own cell niche, as they do in the body," said Stacy Jordahl, a recent chemical engineering Ph.D. graduate from U-M and first author on the paper in Advanced Materials.

The team created a network of fibronectin, a protein that attaches cells to the connective gel. Cells in tissues stretch out the fibronectin, using it a bit like the two-by-fours of a house frame. However, fibronectin tends to coil up if it's not held open. While researchers have used layers of balled-up fibronectin to help cells to attach to previous scaffolds, the protein hasn't been used to full advantage.

Previously, it was painstaking to stretch out fibronectin strands--pulling on them with pipettes, for example--but the new method discovered by the U-M team produces a coating of stretched-out fibronectin without the hard work.

Led by Joerg Lahann, the Wolfgang Pauli Collegiate Professor of Chemical Engineering and director of the Biointerfaces Institute at U-M, the engineers built a grid of microscale cubicles, each half a millimeter to a side. Then, they repeatedly poured a solution containing fibronectin over that surface using a tube that slowly flipped end over end. The tug of the moving liquid was enough to draw the fibronectin out into networks of fibers that interlaced across the whole structure.

"With this engineered way to draw proteins into a network of fibers, we can produce a more natural environment for growing cancer cell cultures that enable us to test drugs or understand cancer biology," Lahann said.

Lahann's team turned the structures over to two cancer researchers, Luker and Max Wicha, the Madeline and Sidney Forbes Professor of Oncology. They used the structures to culture cells that had been removed from breast cancer patients by draining fluid pockets that can accumulate in the abdomen and chest as the disease progresses.

Although cancer cells represent only about 5% of the cells in these fluids, they dominated the cell population after a few days to a week on the fibronectin network. And the cancer researchers were impressed.

"There have been a lot of technologies and approaches devised to try to grow cancer cells in culture that haven't worked so well. Most cancer cells die out when cultured in artificial conditions," Luker said. "In this system, we could pretty consistently grow out the cultures at least for short periods of time."

In addition, the cells seemed to change as they grew on the fibronectin network, becoming more like the kind of cells that are believed to spread cancer to other parts of the body. This could be an advantage for testing cancer drugs, as those cells are most imperative to kill.

However, this bias would hinder experiments exploring cancer biology--for instance, identifying the influences that lead cells to become more aggressive or benign. In the future, the team may investigate whether changes to the way the fibronectin network is structured can remove this bias.
-end-
The study is published in the journal Advanced Materials. The work was funded by the National Cancer Institute, National Science Foundation, Department of Defense and National Institutes of Health.

Luker is also a professor of biomedical engineering and microbiology and immunology. Jordahl is currently a senior engineer at ExxonMobil. Lahann is also a professor of biomedical engineering, macromolecular science and engineering, and materials science and engineering. Wicha is also the director of the Forbes Institute for Cancer Discovery at U-M.

Study: Engineered Fibrillar Fibronectin Networks as Three-Dimensional Tissue Scaffolds

Lahann Lab
Luker Lab

University of Michigan

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.