The tumor microenvironment is comprised of primary cancer cells
mixed with multiple types of stromal cells, of which a significant
fraction originates in the bone marrow. For this reason, bone is an
essential partner for tumor progression. However, it is unclear how
tumor cells co-opt the bone and/or bone marrow to facilitate a
favorable tumor microenvironment.
Among those bone marrow-derived cells in the tumor
microenvironment, a subset of myeloid lineage cells,
myeloid-derived suppressor cells (MDSCs), has been shown to
correlate significantly with tumor progression. MDSCs suppress the
host immune response and infiltrate tumor tissue to promote tumor
growth and angiogenesis. Beyond these critical roles, little is
known about the regulation of MDSCs within bone by distant primary
tumor cells, not to mention therapeutic approaches targeting
MDSCs.
The Park Laboratory aims to address how tumor cells stimulate the
bone microenvironment to regulate MDSCs, contributing to tumor
growth, angiogenesis and/or metastasis.
For this aim, prostate cancer takes a unique position, not only
because of disastrous mortality and morbidity, but also because of
preferential metastasis to the skeleton. Accordingly, prostate
cancer cells secrete numerous important bone-modulating cytokines,
leading to osteoblastic/osteolytic reactions that stimulate the
adjacent bone marrow cells.
We will investigate the molecular mechanism of MDSC activation,
expansion, and/or mobilization within the bone marrow of prostate
tumor hosts. Additionally, we will examine the therapeutic
approaches targeting MDSCs in pre-clinical models with
investigational drugs. The potential research outcomes will promote
understanding of the vicious partnership between cancer and
bone.
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- Vanderbilt-Ingram Cancer Center
Faculty Member
2215 B Garland Ave
1235K MRB IV
Nashville, TN 37232
615-936-7607 (p)
615-343-2611 (f)
MeSH terms are retrieved from PubMed records. Learn more.
Key: MeSH Term Keyword
Apoptosis beta Catenin Blotting, Western Bone Bone Marrow Bone marrow-derived cells Bone Neoplasms Cell Differentiation Clodronic Acid Crk-Associated Substrate Protein Disease Models, Animal Drug Synergism Flow Cytometry Focal Adhesion Kinase 1 Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Hypercalcemia Liposomes Mesenchymal Stem Cells Metastasis Mouse models Mutation NF-kappa B Promoter Regions, Genetic Prostate cancer Proto-Oncogene Proteins c-jun Reactive Oxygen Species Real-Time Polymerase Chain Reaction RNA, Neoplasm Snail Family Transcription Factors Src family kinase Stem Cell Niche Transcription Factors Tumor microenvironment Up-Regulation Wnt Signaling Pathway