Create time: 2020-05-22 11:30:00
In a recent study published in the international journal Journal of Experimental Medicine, scientists from Tel Aviv University found that breast tumors may increase the growth of breast cancer cells by recruiting stromal cells that form in the bone marrow. The findings suggest that recruiting bone marrow-derived fibroblasts may reduce survival in breast cancer patients, and targeting these cells may be promising new therapies for breast cancer.
Source of image: Raz et al., 2018
In solid tumors, cancer cells are often surrounded by other cell types, although not just cancerous cells, which often enhance tumor growth and metastasis. Breast tumors, for example, contain a large number of fibroblasts that promote cancer cell proliferation, inflammation, and the formation of new blood vessels, thereby supplying nutrients and oxygen to growing tumors. Many cancer-related fibroblasts are derived from nearby breast tissue, but others appear to come from other parts of the body.
The researchers found that in breast cancer mice, a large number of cancer-related fibroblasts are derived from bone marrow cells called mesenchymal stem cells (MSCs), and breast tumor tissue can recruit MSCs from the bone marrow and promote its transformation into fibroblasts. These bone marrow-derived fibroblasts are not the same as fibroblasts associated with other cancers, lacking a key cell signaling protein called PDGFRα. But bone marrow-derived fibroblasts can effectively stimulate the production of new blood vessels because they produce a large number of special proteins called tufted proteins. Tumor tissues with bone marrow-derived fibroblasts are often more vascularized and grow faster than those with only breast-derived fibroblasts.
In this study, researchers found that breast cancer contains fibroblasts that lack PDGFRα signaling proteins, suggesting that human tumors may be able to recruit bone marrow-derived cells. In addition, tumors carrying lower levels of PDGFRα tend to be more lethal, suggesting that the recruitment process of bone marrow-derived fibroblasts may be a key step in the progression of breast cancer.
Finally, researcher erez says, we found that the recruitment of bone marrow-derived fibroblasts is essential to promote tumor growth, probably through enhanced blood vessel formation. Understanding the function of these cancer-related fibroblasts may help researchers develop new therapies to jointly target bone marrow-derived fibroblasts and cancer cells themselves.
Yael Raz, Noam Cohen, Ophir Shani, et al. Bone marrow–derived fibroblasts are a functionally distinct stromal cell population in breast cancer. Journal of Experimental Medicine, November 23, 2018, doi:10.1084/jem.20180818