Hijacked Immune Cells Promote Breast Cancer Metastasis
A Lerner Research Institute team has discovered how the regulatory protein kindlin-2 uses immune cells in the breast to advance breast cancer.
Kindlin-2 is an adaptor protein that allows breast cancer cells to communicate with healthy cells in the breast tumor microenvironment, often creating conditions where malignant cells thrive and metastasize, or spread. Adaptor proteins enable communication across the cellular membrane and regulate cellular responses. Specifically, kindlin-2 helps regulate integrin activation. Integrins, receptor molecules found on the surface of cells, are believed to be associated with breast cancer pathogenesis, or development. But the mechanism by which kindlin-2 plays a role in breast cancer metastasis is not yet well defined.
The researchers found in mice that kindlin-2 recruits immune cells, called macrophages, to the tumor site and signals them to secrete growth factors that activate pro-cancer pathways. These events make the breast tumor microenvironment hospitable for the cancer cells and enable them to proliferate and spread. When the team removed kindlin-2 from breast cancer cells via CRISPR/Cas9 technology, the malignant cells became less migratory and invasive.
The team also examined the role of kindlin-2 in human tissues. Researchers compared kindlin-2 expression with outcomes data in 3,500 patients. They found that high levels of kindlin-2 correlate with metastatic potential and poorer prognosis.
The study, published in Cancer Research, was co-led by Khalid Sossey-Alaoui, PhD, and Edward Plow, PhD, both of the Department of Molecular Cardiology. Dr. Plow is chair of Molecular Cardiology and holds the Robert C. Tarazi, MD, Endowed Chair in Heart and Hypertension Research.