July 23, 2015

Targeting bone metastasis

The rigidity of the bone extracellular matrix increases the ability of tumor cells to destroy bone, suggesting new targets for anticancer drug development.

by Henry H. Ong

Many common cancers spread, or metastasize, to the bone. As these metastases destroy bone and are incurable, understanding the underlying molecular mechanism could provide new opportunities for treatment.

Julie A. Sterling, Ph.D., Scott Guelcher, Ph.D., and colleagues in the Center for Bone Biology tested the hypothesis that the bone microenvironment, specifically the rigid mineralized extracellular matrix, stimulates the bone-destroying capacity of tumor cells.

In a study published in the journal Biomaterials, they demonstrated that rigidity enhanced the interaction of a transmembrane receptor, integrin beta 3, with transforming growth factor (TGF) beta receptor type II, and that this, in turn, led to increased expression of tumor-produced factors associated with bone destruction.

In vivo mouse experiments showed that inhibition of integrin beta 3 blocked the tumor’s ability to sense bone rigidity and reduced the expression of the tumor-derived factors. This suggests a promising target for drug development: inhibiting the tumor’s ability to sense the rigidity of the bone microenvironment and preventing integrin and TGF-beta signaling.

This research was supported by the National Institutes of Health (grant CA163499), the National Science Foundation, and by a VA Merit Award.

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