Cancer cell foraging to explain bone-specific metastatic progression.

Abstract

Metastatic cancer is lethal and patients who suffer bone metastases fare especially poorly. Bone-specific metastatic progression in prostate and breast cancers is a highly observed example of organ-specific metastasis, or organotropism. Though research has delineated the sequential steps of the metastatic cascade, the determinants of bone-specific metastasis have remained elusive for decades. Applying fundamental ecological principles to cancer biology models of metastasis provides novel insights into metastatic organotropism. We use critical concepts from foraging theory and movement ecology to propose that observed bone-specific metastasis is the result of habitat selection by foraging cancer cells. Furthermore, we posit that cancer cells can only perform habitat selection if and when they employ a reversible motile foraging strategy. Only a very small percentage of cells in a primary tumor harbor this ability. Therefore, our habitat selection model emphasizes the importance of identifying the rare subset of cancer cells that might exhibit habitat selection, ergo achieve bone-specific metastatic colonization.