Studies have shown that breast cancer enhances its growth by "collecting" cells from the bone marrow.
Studies have shown that breast cancer enhances its growth by "collecting" cells from the bone marrow.
December 10, 2018 Source: Ministry of Science and Technology
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Mouse mammary tumors contain bone marrow-derived fibroblasts (red) as well as other cancer-associated fibroblasts (green).
Image source: Raz et al.
Recently, researchers from Tel Aviv University in Israel found that breast tumors promote their growth by "recruiting" stromal cells that were originally formed in the bone marrow. The study, published in the Journal of Experimental Medicine, showed that the recruitment of bone marrow-derived fibroblasts reduced the survival rate of breast cancer patients, but also suggested that targeting these cells may be an effective treatment for the disease.
For solid tumors, cancer cells are surrounded by other types of cells, and although they are not cancerous cells themselves, they promote tumor growth and metastasis. For example, breast tumors contain a large number of fibroblasts that promote cancer cell proliferation, inflammation, and the formation of new blood vessels, thereby providing nutrients and oxygen to growing tumors. Many of these cancer-associated fibroblasts come from adjacent breast tissue, but others seem to come from other parts of the body.
Neta Erez of the University of Tel Aviv's Sackler School of Medicine and colleagues found that in mice with breast cancer, a large number of cancer-associated fibroblasts are derived from bone marrow cells called mesenchymal stromal cells (MSCs). The researchers found that breast tumors can recruit MSCs from the bone marrow and develop them into fibroblasts.
Image source: Journal of Experimental Medicine
These bone marrow-derived fibroblasts differ from other cancer-associated fibroblasts. For example, they lack a key cellular signaling protein called PDGFRα. However, bone marrow-derived fibroblasts are particularly effective at stimulating the formation of new blood vessels because they produce a large number of proteins called clusterin. Thus, tumors containing bone marrow-derived fibroblasts are more vascularized and grow faster than tumors containing only mammary fibroblasts.
The team found that human breast tumors also contain fibroblasts lacking PDGFRα, suggesting that human tumors may also recruit bone marrow-derived cells. Furthermore, tumors containing lower levels of PDGFRα are more lethal, suggesting that recruitment of bone marrow-derived fibroblasts is a critical step in the progression of breast cancer.
"Our research shows that the recruitment of bone marrow-derived fibroblasts is important for promoting tumor growth," Erez said. "It seems to enhance angiogenesis. Understanding the function of these cancer-associated fibroblasts helps to develop common targets. Bone marrow-derived fibroblasts and new treatments for cancer cells themselves lay the groundwork."
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