Positive Feedback Loops Between Inflammatory, Bone and Cancer Cells During Metastatic Niche Construction.

Bone, which includes several cell populations and numerous cytokines and chemokines that provide cell-cell signaling, is a common destination for many cancer metastases. Bone metastasis skews this signaling to develop vicious cycles between immune, bone and cancer populations that lead to abnormal bone remodeling during cancer niche construction. Temporal models utilize positive feedback systems as an integrative tool providing insights into the rate-limiting processes that determine multiple stages of the bone metastasis. We develop a logical-transient-threshold framework by linking temporal responses of the cancer, bone and immune systems through macrophages during ecological niche construction of cancer in host bone.