Functions of IL-1alpha and ESE-1 in Reactive Stroma Modulation of the Immune Landscape in Prostate Cancer
Abstract
The purpose of this project is to understand the role and mechanisms of IL-1alpha in regulating the ontogeny and differentiation of mesenchymal stem cells (MSCs) to immune reactive fibroblasts in prostate cancer. Aim 1 is to address ontogeny of immune reactive fibroblasts from perivascular MSCs. Aim 2 is to address the role of the ELF3 transcription factor. Aim 3 is to address how the recruitment and biology of immune reactive fibroblasts regulate the immune landscape in experimental tumors. Progress has been made in engineering prostate cancer cells for overexpression of IL-1alpha and in knocking down ELF3 expression in MSCs. We have generating three-dimensional organoids as proposed. We have also generated the NG2-cre/Esr1*/ R26-stop-EYFP and the NG2-cre/Esr1*/ R26-stop-EYFP / Elf3 fl/fl mice, which have now been backcrossed (10 generations) into the C57BL/6 background. We have been successful in generating allograft tumors of TRAMP C1D cancer cells in the reporter mice. We were able to show that perivascular MSCs are the source of the IL-1alpha induced fibroblasts in vivo and that ELF3 mediates IL-1alpha action. Progress has been made in each Aim.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2018
- Accession Number
- AD1062554
Entities
People
- David R. Rowley
Organizations
- Baylor College of Medicine