Decoding reciprocal extracellular matrix-tumor cell interactions in pediatric rhabdomyosarcoma
Patients with metastatic solid tumors, such as rhabdomyosarcoma (RMS), continue to suffer from dismal patient outcomes. Innovation for treating these patients is hampered by our limited understanding of how RMS cells detach from tumors and seed metastatic sites. Our laboratory are leaders in the study of the complex cellular architecture of RMS. In prior work, we identified the broad range of cell types within RMS and are now in a position to translate those results. In preliminary work, we have developed an easy-to-perform and replicable system to model the process of cell detachment. We will use this system to understand how RMS cells adapt to and grow when detached from the tumor surface. In addition, we will identify how RMS cells directly change the cellular environment around them, or alternatively, how they recruit normal tissue cells to indirectly remodel the tissue environment. If successful, we will establish new methods to study RMS metastasis, and we will identify new targetable pathways in metastatic RMS lesions for therapeutic intervention.
Project Goals
The goals of this proposal are two-fold: (1) using an easy-to-implement model of tumor detachment in rhabdomyosarcoma (RMS), we will study how RMS cells survive and change when detached from the surface of a tumor; and (2) using a combination of experimental models and patient samples, we will investigate how RMS cells influence the surrounding tissue at metastatic lesions. The experiments in this proposal will lay the groundwork for future efforts to block these processes, with the ultimate hope of developing new therapeutic approaches for the treatment of metastatic RMS.
