(570h) A Mathematical Model of Tumor-Induced Bone Disease Based On the Vicious Cycle Concept

Tumor cells grow in specific metastatic sites because of molecular interactions that occur between tumor cells and their microenvironment. Several tumor cells such as breast and prostate cancers frequently metastasize to bone where they release factors that cause bone destruction thwarting normal bone remodeling. During the bone destruction, growth factors are released from bone matrix that stimulate further growth of the tumor cells and subsequently more bone resorbing factors are released from the tumor cells. In order to understand underlying mechanism of this “vicious cycle”, a mathematical model has been developed based on a recent mathematical model of bone remodeling by Komarova et al. [1]. Our model describes the dynamics of cell population and cell-cell interactions among osteoclasts, osteoblasts, and tumor cells within a single bone modeling unit where the net effects of local factors on the rates of cell populations have been approximated using power law relations. Tumor burden and bone mass change calculated from the model are compared to values obtained from experiments in which MDA-MB-231 cells, a human cell line that preferentially metastasizes to bone, were injected directly into the tibiae of mice. It is found that the model captures the autocatalytic mechanism of bone destruction observed experimentally, demonstrating at least qualitative validation of the model.

[1]        Komarova SV, Smith RJ, Dixon SJ, Sims SM, Wahl LM. Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling. BONE 2003;33: 206-215.