Career oncology researchers are experiencing one of the great evolutions in life sciences: the transition from 2D to 3D cell cultures.
As cancer investigators continue to glean the reconstructive benefits of 3D models' in vivo-like contexts for their investigations, those learnings have yielded a better understanding of how — and why — 3D is superior to 2D when creating cancer microenvironments.
Breast cancer microenvironments are no exception.
Think of a cancer microenvironment as a complete ecosystem that sustains cancer cells in a tumor. The environment includes not only biological material, such as the cancer cells and the extracellular matrix, but also response triggers, such as mechanical cues and biochemical signals.
One reason researchers are so keenly interested in studying cancer microenvironments is because of their utility in understanding cancer progression. Cues from multiple areas of the tumor's biological context, such as the cellular makeup of the microenvironment and its biochemical properties, can cause the tumor to spread. Having a full view of the tumor's potential metastatic behavior means that anti-cancer agents can be studied and tested in similar circumstances to the in vivomalignancy.
This matters because the majority of cancer deaths are caused by metastasized cancers, rather than origin tumors. That's especially true of breast cancer: Metastatic breast cancer causes most of the 42,000 annual deaths from breast cancer.
Protecting the integrity of the microenvironment can help replicate the metastatic nature of the tumor as it moves from formation and angiogenesis to invasion, intravasation, extravasation, and, ultimately, circulation.
As with other areas beyond oncology, researchers continue to find that 3D cell cultures better reconstruct the behaviors and properties of native tissue, especially with regard to cell morphology. 3D cultures enable integrin-mediated adhesions around the entire surface of the cell, whereas 2D cultures, which are inherently flat, are limited to just one side.
In breast cancer microenvironment applications, Frontiers in Bioengineering and Biotechnology describes 2D as a "practical but incompetent" platform. The 2D platform has merit, as it's inexpensive and potentially faster, but it might not fully represent the biological, chemical, and immunological makeup and response of native material.
Converting the culture to a 3D analysis by adding hydrogel scaffolding, such as Corning® Matrigel® matrix, can greatly enhance the breast cancer microenvironment's usefulness in the lab, thanks to near-native morphology, proliferation, metabolism, and agent response.
Just as the bench evolved from 2D to 3D, so, too, has it evolved to bridge the gaps inherent in in vitro culturing. That's where 3D bioprinting comes in.
As an advanced approach for recreating environments, 3D bioprinting is a product of modern 3D printing technology and bioinks that usually come from one of three categories: extrusion, inkjet or laser printing. Because 3D bioprinting can produce biological materials at a cellular level, researchers posit that the technology could become ubiquitous for breast cancer microenvironments, even more than body-on-a-chip or synthetic tissue.
Research into 3D bioprinting — including the possibility of hybrid printing or post-crosslinking — is still ongoing. As those investigations continue, it's clear that native and synthetic scaffolding, as well as the permeable supports to hold them, will have an exciting role to play.
And for the thousands of breast cancer patients whose lives might someday depend on those very developments in the lab, these advancements could make all the difference.
