Effects of Three Dimensional Microenvironment on Tumorigenicity of Fibrosarcoma in vitro

Abstract

Tumor microenvironment plays an important role in cancer progression owing to
interactions between the tumor and adjoining cells and, as in bone marrow, the unique architecture
and chemical compounds that characterize it. It has recently been proposed that
bone marrow shelters cancer cells in niches which may favor regulation of their quiescence,
although the mechanisms involved have yet to be elucidated. We conjectured that a bone marrow
mimicking, calcium providing 3D biolattice recently developed by our group could affect
fibrosarcoma cells in various ways, whether via its specific architecture or due to its provision
of calcium, an element correlated with many tumorgenic processes. In order to verify our
conjecture, we examined the modifications induced in fibrosarcoma cells by this biolattice.
We found that its regulatory effects on fibrosarcomas enhanced tumorigenicity, mediated by
up-regulated tumorigenesis related genes. We observed decreased proliferation of cancer cells
accompanied by up-regulation of genes associated with cancer stem cells, pointing to a process
of de-differentiation. In addition, our results revealed up-regulation of Wnt4 and c-Myc in cells
cultured on the biolattice, along with down-regulation of AXIN-1 and WIF-1. Taken together
these findings suggest that a calcium rich bone marrow-like microenvironment can affect the
tumorigenic capacity and fibrosarcoma cells de-differentiation through the mediation of the
Wnt signaling pathway.