Bone Abstracts

Several cell types form the hematopoietic stem cell niche. These niches sometimes become hijacked by cancer cells, which may later form metastatic lesions. Our aim was therefore to characterize the bone marrow microenvironment to affect cancer cell homing to bone marrow.

Pharmacologic modification consisting of PTH to stimulate the osteoblasts and zoledronic acid to prevent the increase in osteoclasts through PTH resulted in increased homing of cancer cells to the bone marrow 24 h after intracardiac injection of MDA-MB-231 cancer cells. Hematopoietic stem and progenitor cells numbers remained unchanged. Instead, we found a negative correlation between cancer cell homing and the decrease in mesenchymal stromal cells (MSC) (r=−0.59, P<0.001, n=40). Evaluation of a conditional knockout of β1 integrin in the bone marrow confirmed an association between diminished homing and increased MSCs. We next labeled and introduced MSCs into immune-deficient mice to determine the effect of increasing MSCs in the bone marrow. The labeled cells in the bone marrow correlated with the numbers injected. In addition, the more cells were detected in the bone marrow the less cancer cells homed to the bone marrow.

We then asked whether MSCs could be used as a prognostic marker for bone metastasis. In a cohort of prostate cancer patients, we found a correlation between the percentage of MSCs and the presence of epithelial cells in the bone marrow (r=−0.47, P<0.005, n=35). In addition, the percentage of MSCs by flow cytometry was threefold lower in patients with epithelial cell in the bone marrow than those without such cells.

These data suggest that either a lower number of MSCs is associated with more “space” for cancer cells to settle in the bone marrow, or that MSCs inhibit cancer cell homing. It is tempting to conclude that modification of MSCs might prevent cancer cells from homing to bone marrow.