Researchers at Georgia Tech have developed a method for producing large and inverted organoids useful for studying the early phases of ductal carcinoma in situ (DCIS) breast cancer. Organoids are miniaturized and simplified 3D versions of organs produced in vitro that mimic micro-anatomy. They are useful for studying diseases and their treatments in laboratories.
In DCIS, breast cancer cells reside within the lumen of ducts on the side of the epithelium opposite the basement membrane. An organoid platform with an inverted orientation (also known as a basal-in phenotype) provides direct access to the epithelial surface opposite the basement membrane, significantly aiding in the study of DCIS cancer progression.
Georgia Tech researchers determined that having the epithelial cells self-assemble around and encapsulate a minimal gel scaffold plays a critical role in the inverted phenotype and provides easy lumen access. This cell-assisted scaffolding enables cells to self-organize into patterns with distinct cancer cell populations both inside and at the periphery of the epithelial organoid.
- Innovative: Serves as a convenient platform for studying the invasive abilities of breast cancer cells
- Stable: Enables formation of large inverted organoids where the basement membrane forms on the interior surface alongside a breast cell line epithelium
- Flexible: Allows for long-term studies of at least 25 days due to the robust maintenance of the inverted orientation
- Drug discovery
- Drug screening
- Personalized medicine
- Xenograft alternatives
In vitro cancer models are highly sought after as low-cost alternatives to investigate basic cell functions, such as proliferation and invasion, in addition to providing high-throughput platforms for drug-screening. While a variety of platforms exist—ranging from Transwell migration assays to 3D microfluidic models—3D spheroid/organoid cultures are of particular interest for their ability to be grown in co-cultures for long durations if needed, used for high-throughput screens, and applied as patient surrogates for precision drug testing. Organoids that mimic physiological cell heterogeneity, basement membrane structures, and 3D cellular organization are particularly valuable.
While recent advances in breast cancer organoids derived from patients have been impressive, the small lumens of organoids and cell-filled spheroids make invasion studies difficult. This Georgia Tech innovation is envisioned to open new opportunities for convenient, standardized, and physiological cancer cell invasion studies.
Comparison of inverted mammary organoids to existing co-culture models. Schematic of (a) multicellular spheroid model and (b) inverted organoid model.