Fibroblasts play a role in the spread of cancer, and a recent study showed that mammary tumors can stimulate their growth by recruiting mesenchymal stromal cells derived from the bone marrow for primary bad tumors.
Fibroblasts play a role in the spread of cancer, and a recent study showed that mammary tumors can increase their growth by recruiting mesenchymal stromal cells derived from the bone marrow (MSC) to primary bad tumors and lung metastases and differentiating a different subpopulation of cancer. Associated fibroblasts (CAFs).
These cells could be a new target for drug development, the researchers said.
Within solid tumors, cancer cells are surrounded by other types of cells that, although not cancerous, stimulate tumor growth and metastasis. Breast tumors contain a large number of "resident" fibroblast cells that promote the proliferation of cancer cells, inflammation and the formation of new blood vessels to supply nutrients and oxygen to the growing tumor.
Many of these fibroblasts badociated with cancer are derived from neighboring bad tissue, but others seem to come from other parts of the body.
The study by the Sackler School of Medicine, Tel Aviv University, found that in mice with bad cancer, fibroblasts derived from the bone marrow are effective to stimulate the formation of new blood vessels because they produce large amounts of a protein called clusterin. Therefore, tumors containing fibroblasts derived from the bone marrow were more vascularized and grew faster than tumors that only contained fibroblasts derived from the bad.
These fibroblasts derived from the bone marrow are different from other fibroblasts badociated with cancer; for example, they lack a cellular signaling protein called PDGFRα, unlike resident CAFs. Recruitment of the stromal cells resulted in a decrease in the percentage of CAF expressing PDGFRα. The decrease in PDGFRα in patients with bad cancer was badociated with a worse prognosis, suggesting that CAFs derived from BM may decrease survival.
According to the researchers, the expression of PDGFRα distinguishes between 2 functionally unique CAF populations in bad tumors and metastases, the finding could have implications for patient stratification and precision therapies. However, the therapeutic selection of CAFs remains a challenge as a result of incomplete knowledge of their origin and functional contribution.
"Our study shows that the recruitment of bone marrow-derived fibroblasts is important to promote tumor growth, probably by increasing the formation of blood vessels," said Neta Erez, PhD, of Sackler's Department of Tumor Biology, in a statement. "Understanding the function of these fibroblasts badociated with cancer could be the basis for developing new therapeutic manipulations that target fibroblasts derived from the bone marrow, as well as the cancer cells themselves."
Raz Y, Cohen N, Shani O, et al. Fibroblasts derived from the bone marrow are a population of functionally distinct stromal cells in bad cancer [published online November 23, 2018]. J. Exp. Medicine. doi: 10.1084 / jem.20180818.