Short background
Cells of the tumor microenvironment control tumor growth, metastasis and treatment response. These aspects of tumor biology are well studied in tumors derived from epithelial cells, but are sparsely described in sarcomas. This study focuses on how cellular crosstalk in pediatric rhabdomyosarcoma (RMS) regulates tumor behavior. RMS is the most common soft-tissue sarcoma of childhood and displays features of skeletal muscle differentiation.

Aims and objectives
The overall aim is to identify useful biomarkers and characterize the crosstalk between nonmalignant cells and RMS tumor cells to uncover pathways and mechanisms of potential therapeutic relevance.

We aim to:

1. Characterize how RMS tumor cells reprogram stromal cells to lose their tumor-suppressive functions during early tumor development

2. Characterize how tumor-naïve stromal cells suppress RMS tumor growth

3. Investigate whether oncogenic crosstalk between tumor cells and stromal cells is regulated by the PDGF, TGFbeta or IGF pathways

Main approach and methods
The project will be guided by the existing results from a gene expression analysis of bidirectional crosstalk between tumor cells and stromal cells. The preliminary findings show that RMS tumor cells reprogram normal tumor growth-suppressive stromal cells to display a “pseudo-tumor cell” phenotype, where the stromal cells gain tumor cell properties. The tumor growth-suppressive effects of tumor-naïve stromal cells on tumor cells have in turn been characterized by gene expression analysis of RMS tumor cells. The experiments provide evidence for a role of stromal cells in the regulation of RMS tumor behavior.

Planned studies include functional analysis of identified candidate biomarkers in cells and patient material. Methods to be used include various cell culture assays, quantitative PCR, immunohistochemistry and microscopy.