CXCL14/ACKR2 signaling in the tumor microenvironment enhance metastasis and shorten survival of breast cancer patients
In the present study Elin Sjöberg and colleagues in the Arne Östman research group have identified that cancer associated fibroblast (CAF)-produced CXCL14 re-activates a developmental program that promote migration and invasion of cancer cells, leading to increased formation of lung metastasis in mice. They also identified a novel CXCL14-signaling component, ACKR2, which is important for the tumor-promoting effects of CXCL14.
Solid tumors are composed of multiple cell types and molecules that communicate with the cancer cells to promote growth of the tumor and progression of the disease. The cells and molecules surrounding the cancer cells in a tumor is called the tumor microenvironment, and one of the most common cell types in the tumor microenvironment is CAFs. CAFs produce factors that can influence tumor growth, invasion into surrounding tissue, and spread of cancer cells into the circulation. Circulating cancer cells will eventually exit the blood stream and enter distant organs where growth of daughter tumors, metastasis, can appear. One factor produced by CAFs in breast cancer is CXCL14. How CAF-derived CXCL14 promote tumor progression and metastasis formation has not previously been shown.
Clinical relevance was obtained by analyzing the levels of CXCL14 and ACKR2 in tumors of breast cancer patients. Combined gene expression of CXCL14 and ACKR2 was significantly correlated to worse survival of the patients. This novel CXCL14/ACKR2 pathway should be explored as a therapeutic target for treatment of breast cancer patients.
A Novel ACKR2-Dependent Role of Fibroblast-Derived CXCL14 in Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer.
Sjöberg E, Meyrath M, Milde L, Herrera M, Lövrot J, Hägerstrand D, et al
Clin. Cancer Res. 2019 Mar;():