Could Halting Cancer Cell Motility Stop Metastasis in Its Tracks?

Cancer wouldn't be able to spread if its cells couldn't independently detach, invade other areas of the body, and establish new cellular colonies. So it tracks, then, that targeting cellular motility could stop metastasis—an application that could offer new hope to millions of cancer patients.

That's why researchers continue to investigate the preclinical applications of motility-interrupting treatments for metastatic cancers, particularly for use in personalized medicine. The use of 2D cultures lets scientists conduct genetic and pharmacological screenings, while 3D models expand that promise in new ways by using extracellular matrices (ECMs) to establish recapitulating in vivo architectures.

Opportunities abound in cellular motility research, says Shabana Islam, Ph.D., a product line manager at Corning Life Sciences, and there are myriad assays to assess the role of cell motility in how tumors metastasize.

"The optimal approaches to inhibit cell motility to preempt metastasis depend on the type of cancer, where it has spread, previous treatments, and a patient's general health," Islam says.

Most oncological motility studies, in some way, study cellular evolution from detachment at the cancer's origin point to adhesion elsewhere in the body—and there's often a great deal of overlap between the many steps involved in that process.

Cell Migration and Invasion with Transwell Permeable Supports

In vitro cell migration and invasion assays are frequently used as model systems to quantify the directed movement of cells towards a chemoattractant stimulus or to measure how a particular drug, antibody or extracellular matrix (ECM) coating affects movement of cells.

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Understanding Metastasis

Cancer metastasizes in four steps:

Detachment: Cancer cells detach from the tumor's origin point by breaching the basement membrane, either by degrading it or pushing it aside.
Migration: Cancer cells move to a new area—either to local tissue or nearby lymph nodes, organs, or tissues—through blood and lymphatic vessels.
Invasion: Tumor cells break through ECMs into a new area.
Adhesion: Cells reattach and integrate into the new environment.

Though each step involves separate mechanisms, they're interrelated; inhibiting any one of them could disrupt the entire process and help keep malignancies local—and, hopefully, more treatable and survivable. Researchers studying metastasis, then, will need to analyze the spreading sequence step by step.

"If you're looking at invasion, you'll also need to look at migration and adhesion," Islam says. "And same with migration—you can't look at just the movement of cells without also studying the detachment, invasion, and adhesion."

The Right Tools to Tackle Metastasis

Given the overlaps inherent in cell motility research, Islam notes the value of permeable supports, which are akin to an all-in-one vessel and can be coated with ECMs. Keeping experiments contained in the same cultureware also negates the need to transport material between steps, Islam adds.

Different pore sizes of permeable supports support different research goals. Migration studies will typically use 3-micron to 5-micron supports, which could be uncoated or coated with fibronectin (an attachment factor), whereas invasion studies usually use precoated 8-micron supports, Islam explains.

If you're conducting 3D cellular research, Islam says, you'll need an extracellular matrix to grow the organoids. But, she adds, "you'll also need it when studying cell invasion, since cancerous cells must cross that ECM barrier to metastasize."

Researchers conducting high-throughput screening should also consider Corning® FluoroBlok™ Cell Culture Inserts, which can save the time and hassle of swabbing and scraping the ECM layer to count cells involved in migration and invasion assays. The inserts also block light transmission between 400 and 700 nanometers.

The Promise of 3D Research

As the prominence of cell motility research grows, 3D models could fill knowledge gaps in many areas, including those studying the role of cell motility in how cancer spreads.

"No one assay will give the complete answer," Islam says. "Scientists will still need to validate, and people will need to assess historical research data and experiment from there. Still, 3D individual in vitro organoids for personalized medicine hold great promise in the years ahead because of their ability to recapitulate the 3D environment for projects involving both basic and therapeutic science."

That's not to say that 2D experiments don't have value.

"One limitation with organoids is blood vasculature, which is an essential component for those studying cell migration and invasion," Islam says.

And yet the pace of technology has quickened so much that breakthroughs are coming faster and more frequently than ever. You never know what could be waiting around the corner.

"Technologies are continuously evolving," Islam says. "Researchers should stay current with new updates and technologies, attend scientific conferences, and just see what's out there that could support their work in new ways."

Could Halting Cancer Cell Motility Stop Metastasis in Its Tracks? | 3D Cancer Cell Models | Corning