In-situ collagen mineralization modulates metastatic properties of breast cancer cells.

Abstract

Bone metastasis is the leading cause of morbidity and mortality in advanced-stage breast cancer patients. While most studies focus on the cellular and genetic factors associated with breast cancer metastasis, the role of the extracellular matrix (ECM) of bone in breast cancer metastasis remains elusive. In this study, we recapitulated the bone microenvironment using in-situ mineralized collagen type-I hydrogels and utilized them to understand breast cancer metastasis. Our results indicated successful mineralization of collagen type-I based hydrogels in the presence of serum proteins, which increased as a function of time. There was no difference in the adhesion of breast cancer cells seeded on collagen and mineralized collagen surfaces. However, there was a marked reduction in cell proliferation, down-regulation of various metastatic markers, and decreased migratory phenotype with a concomitant increase in cleaved caspase-3 on mineralized collagen compared to collagen hydrogels. In conclusion, our results suggest an inverse relationship between bone mineralization and the metastatic propensity of breast cancer cells. We further speculate the role of other factors in the skeletal ecosystem for mediating preferential homing of breast cancer cells to the bone microenvironment.