Study Finds Behaviors of Breast Cancer Cells Help Predict Risk of Bone Metastasis

Findings published in PLoS ONE showcase an in vitro cancer model to investigate why breast cancer spreads to bone. The investigators are optimistic that the method holds promise for advancing the development of preclinical tools to help predict breast cancer bone metastasis.^1,2

Image credit: Sebastian Kaulitzki | stock.adobe.com

There are about 2.3 million new cases of breast cancer and 700,000 deaths every year, and approximately 80% of patients with primary breast cancer are able to be cured if diagnosed and treated promptly. In many cases, according to the investigators, the cancer has already spread to other parts of the body at the time of diagnosis. Metastatic cancer is often incurable and makes up over 90% of deaths related to cancer.¹

Because there are no in vitro models to study how breast cancer can spread to secondary organs, including bone, lungs, liver, or brain. For this study, the investigators created a novel model that uses invasion/chemotaxis (IC)- and extravasation (EX)-chip platforms to model a bone-like cellular microenvironment that consists of cell lines that represent osteoblasts, stromal cells, and monocytes embedded in 3D collagen I-based extracellular matrices.^1,2

The IC- and EX-chips allowed the investigators to visualize and quantify the invasion and extravasation potentials of metastatic breast cancer cell line MDA-MB-231 toward lung, liver, and breast microenvironments. The investigators also tested the platforms with MDA-MB-231 clones LM2 and BoM 1833, which specifically metastasize to lung and bone, respectively, in mouse models.²

The study authors demonstrate that the invasion and extravasation potentials of the MDA-MB-231 clones toward the microenvironment on IC- and EX-chips correlate with their in vivo behaviors, and these platforms allow a straightforward approach to providing in vitro data representative of in vivo bone metastasis risk for breast cancer cell lines. The investigators note that if further improvements to the tested platforms are made, they can allow for the analysis of clinical samples and develop site-specific clinical approaches.²

“Breast cancer most frequently spreads to bone, with an estimated rate of 53%, resulting in severe symptoms such as pain, pathological bone fractures, and spinal cord compressions. Our research provides a laboratory model that estimates the likelihood and mechanism of bone metastasis occurring within a living organism. This advances the understanding of molecular mechanisms in breast cancer bone metastasis and provides the groundwork for developing preclinical tools for predicting bone metastasis risk,” Burcu Firatligil-Yildirir, postdoctoral researcher at Tampere University, said in a news release.¹

In addition to the correlations found between the behaviors of the MDA-MB-23 breast cancer cells on the chip models and their in vivo potential, the culture model also shows that collagen I can offer a better bone-like environment of bone cells and matrix composition, and stiffness regulate the invasion of breast cancer cells. According to the authors, using in situ contactless rheological measurements under cell culture conditions showed a presence of cells that increased the stiffness values for matrices up to 1200 Pa after being monitored for 5 days. This suggests that the cellular composition has a significant effect on the regulation of matrix mechanical properties, which can contribute to the invasiveness.²

According to the investigators, the evaluated platforms can allow for the investigation of underlying molecular mechanisms that are present in breast cancer bone metastasis, therefore, providing groundwork to develop preclinical tools to predict the risk of bone metastasis. Additionally, they note that developing sustainable in vitro models that mimic the native breast and bone microenvironments’ complex natures is a multidisciplinary challenge.^1,2

“Our work shows that physiologically relevant in vitro models can be generated by combining cancer biology, microfluidics and soft materials. The results open new possibilities for developing predictive disease, diagnostic and treatment models,” Nonappa, associate professor and leader of the Precision Nanomaterials Group at Tampere University, said in the news release.¹

REFERENCES

1. Tampere University. Study shows why breast cancer spreads to bone. News release. October 18, 2024. Accessed October 30, 2024. https://www.eurekalert.org/news-releases/1061808

2. Firatligil-Yildirir B, Bati-Ayaz G, Nonappa, Pesen-Okvur D, Yalcin-Ozuysal O. Invasion/chemotaxis- and extravasation-chip models for breast cancer bone metastasis. PLoS ONE. 2024;19(10):e0309285 doi:10.1371/journal.pone.0309285