Stroma composition in tumors often has a significant impact on tumor growth and treatment response, and ultimately, patient overall survival. The importance of stroma in sarcoma is, however, largely unknown. In the “Stroma in Sarcoma (SiS)” project, we explore the role of infiltrating stroma cells in human soft-tissue sarcoma (STS) with a focus on pediatric rhabdomyosarcoma (RMS). RMSs are rare, heterogeneous tumors recognized for their skeletal muscle differentiation status.
We have together with our international collaborators investigated the tumor biology linked to platelet-derived growth factor (PDGF) signaling in pediatric RMS (Ehnman et al., Cancer Research, 2013). PDGF receptors are recognized for their oncogenic properties in many tumors and are also therapeutic targets in advanced STS. PDGF receptors are expressed in tumor cells and/or stroma cells in subsets of RMS. Our work shows that PDGF receptor β expression in stroma correlates with the more aggressive alveolar subtype and with metastasis in children.
Our ongoing projects involve translational and experimental studies on PDGF receptors, tyrosine kinase activity, cancer stem cells, immunology and angiogenesis. The experimental methods we use in the lab include, among others, primary cell culture (2D, 3D, coculture), immunostaining (human and mouse tissue), advanced microscopy, fluorescence-activated cell sorting (FACS), quantitative real-time PCR as well as other gene-expression methods.
For further information, please contact Monika Ehnman.
Selected publications on stroma in sarcoma:
1. Ehnman, M., et al., Distinct effects of ligand-induced PDGFRalpha and PDGFRbeta signaling in the human rhabdomyosarcoma tumor cell and stroma cell compartments. Cancer Res, 2013. 73(7): p. 2139-49.
2. Ehnman, M. and A. Ostman, Therapeutic targeting of platelet-derived growth factor receptors in solid tumors. Expert Opin Investig Drugs, 2014. 23(2): p. 211-26.
3. Paulsson, J., M. Ehnman, and A. Ostman, PDGF receptors in tumor biology: prognostic and predictive potential. Future Oncol, 2014. 10(9): p. 1695-708.
4. Ehnman, M. and O. Larsson, Microenvironmental Targets in Sarcoma. Front Oncol, 2015. 5: p. 248.