Effects of Three Dimensional Microenvironment on Tumorigenicity of Fibrosarcoma in vitro

Irit Levinger, Racheli Zagouri, Yvonne Ventura and Razi Vago*

Effects of Three Dimensional Microenvironment on Tumorigenicity of Fibrosarcoma in vitro.
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. Many studies highlight the importance of calcium in regulating cancer development and progression.

Cancer Stud Mol Med Open J. 2014; 1(1): 16-26. doi: 10.17140/CSMMOJ-1-103