A recent study published by UC Berkeley bioengineers found that tumor cells can invade and migrate in brain tissue using long “microtentacles” attached to the cells.
The study, published in the Proceedings of the National Academy of Sciences on May 26, used high-resolution imaging to observe how tumor cells interacted with a three-dimensional matrix similar to brain tissue.
The researchers also used tumor cells derived from patients with glioblastoma, the most common form of brain cancer. According to the study, glioblastoma is characterized by the slow diffusion of tumor cells into healthy brain tissue, which poses challenges to both surgical and medicinal remedies.
Describing the initial motivations behind the study, campus bioengineering professor Sanjay Kumar said in an email that his lab had previously shown that glioblastoma cells attach to hyaluronic acid, a sugar-based polymer found in brain tissue, “in order to gain a foothold on the surrounding tissue.”
Key to this attachment is a receptor called CD44, which also plays an important role in the progression of other cancers, such as breast and pancreatic cancer, according to Kumar.
Kayla Wolf, the study’s lead author and a campus alumna, observed that the glioblastoma cells introduced to their matrix developed long, tentacle-like structures that extended tens of micrometers from their bodies and were used to move around, Kumar said. Furthermore, these microtentacles were able to adhere to the matrix via the CD44 receptor, according to the study.
“Dr. Wolf provided critical intellectual leadership from start to finish, including noticing the microtentacles, recognizing the connection to microtubes and structures previously seen in circulating tumor cells, and carrying out the majority of the work,” Kumar said in the email.
Wolf also recognized that the long protrusions seen in glioblastoma cells were similar in structure to microtentacles found in breast cancer cells circulating in blood, added study co-author Poojan Shukla.
In addition to elucidating how these microtentacles help tumor cells move, the study identified several proteins involved in this mechanism that show potential as glioblastoma drug targets.
Shukla added that CD44 remains of interest in the lab, as well as the general research direction of building biomaterials platforms to better understand how cancer cells move through tissue.
A key strength of the lab is materials engineering and being able to make synthetic, gel-based matrices to study tumors in, according to Shukla.
“Because the gels we made are versatile, they can be tuned to different stiffnesses or protein compositions to examine other hypotheses about cell motility,” Shukla said in an email.
According to Kumar, his lab is continuing to build on the work done in this study. More evidence is needed to prove that the microtentacles they observed on glioblastoma cells are important in tumor growth, he added.