Breast Cancers Recruit Cells From Bone Marrow to Increase Their Growth, Study Says

Fibroblasts play a role in the spread of cancer, and a recent study showed that breast tumors can boost their growth by recruiting bone marrow—derived mesenchymal stromal cells (MSCs) to primary breast tumors and to lung metastases and differentiate a distinct 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 cell types that, though not cancerous themselves, boost tumor growth and metastasis. Breast tumors contain large numbers of “resident” fibroblast cells that promote cancer cell proliferation, inflammation, and the formation of new blood vessels to supply the growing tumor with nutrients and oxygen.

Many of these cancer-associated fibroblasts are derived from the neighboring breast tissue, but others seem to come from elsewhere in the body.

The study from the Sackler School of Medicine, Tel Aviv University, discovered that in mice with breast cancer, the marrow—derived fibroblasts are effective at stimulating the formation of new blood vessels because they produce large amounts of a protein called clusterin. Tumors containing bone marrow–derived fibroblasts were therefore more vascularized and grew faster than tumors that only contained breast-derived fibroblasts.

These bone marrow—derived fibroblasts are different from other cancer-associated fibroblasts; for instance, they lack a cell signaling protein called PDGFRα, unlike resident CAFs. The recruitment of the stromal cells resulted in a decrease in the percentage of PDGFRα-expressing CAFs. Decrease in PDGFRα in patients with breast cancer was associated with worse prognosis, suggesting that BM-derived CAFs may decrease survival.

Since PDGFRα expression distinguishes between 2 functionally unique CAF populations in breast tumors and metastases, the finding could have implications for patient stratification and precision therapeutics, the researchers said. However, therapeutic targeting 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 for promoting tumor growth, likely by enhancing blood vessel formation," said Neta Erez, PhD, from Sackler’s Department of Tumor Biology, in a statement. "Understanding the function of these cancer-associated fibroblasts could form the basis of developing novel therapeutic manipulations that co-target bone marrow—derived fibroblasts as well as the cancer cells themselves."

Reference

Raz Y, Cohen N, Shani O, et al. Bone marrow—derived fibroblasts are a functionally distinct stromal cell population in breast cancer [published online November 23, 2018]. J. Exp. Med. doi: 10.1084/jem.20180818.