The Tumor Biology and Metastasis Branch (TBMB) supports research that seeks to understand the interactions of cancer cells within the tumor and/or with the host microenvironment in order to delineate the molecular mechanisms and signaling pathways of tumor angiogenesis and lymphangiogenesis, cell motility and invasion, tumor progression, and metastasis. The Branch also supports research on the role of the microenvironment (stroma) created by inflammation and the inflammatory signaling molecules in tumor formation and progression, the effects of hypoxia on invasion and metastasis, the role of somatic stem cells in determining tumor progression and metastatic behavior, and control of the stem cell niche by tumor microenvironment.
Emerging areas of science supported by the Branch include: epigenetic silencing of stromal genes in precancerous and cancerous lesions; tumor dormancy and the role of tissue microenvironment in activating dormant cells; the role of bone marrow-derived progenitor cells in tumor formation, invasion or metastasis; the conferring of therapeutic resistance; the molecular mechanisms of organ specific metastasis; and the heterogeneity of the extracellular matrix within the tumor microenvironment and changes during tumorigenesis, progression and metastasis.
Areas of research in this program include tumor-stroma interaction, inflammation, stem cell-stromal cell niche interactions, tumor metastasis, cell fusion, tumor-stroma metabolism, stem cell niche and tumor dormancy, and the role of tumor microenvironment in the establishment of the premetastatic and metastatic niche. Key areas also include research on the role of tumor stroma in promoting tumor cell migration, proliferation, survival, angiogenesis, tumor progression and the role of EMT in tumor initiation-progression-metastasis continuum. It also supports the development of appropriate new animal, cellular or organotypic models to study tumor stroma interactions. Also included are studies on the role of exosome secretion by tumor cells, and cell fusion in promoting an aggressive cancer phenotype.
- Gradients and Flow of Soluble Factors in the Microenvironment
Key areas include molecular characterization of the heterogenous distribution of cells and soluble factors in the microenvironment and their role in tumor cell adhesion, migration, invasion, intravasation, inflammation, progression and metastasis.
- Stem Cell Niche, Tumor Microenvironment and Tumor Dormancy
Key areas include studies on the role of somatic stem cells in determining tumor progression and metastasis; stem cell niche- tumor stroma interactions and its impact on tumor dormancy; molecular characterization(s) of changes in stem cells that confer invasive, migratory, and/or metastatic phenotype(s); overlapping features of EMT and tumor initiating cells.
- Metabolism and Tumor Progression
Key areas include the role of tumor and stromal cell metabolism during cell migration, angiogenesis, inflammation, and tumor progression.
- Microbiome and the Tumor Microenvironment
Key area includes interaction(s) of microbiome with host cells and its role in modulating tumor progression, metastasis and therapeutic resistance.
- Bone Microenvironment and Bone Metastasis
Key areas include research in bone microenvironment and metastasis. This includes the role of cell adhesion molecules, proteases, hormones, and paracrine growth factors in promoting the survival of metastatic tumor cells in the bone microenvironment. Research involving inflammation, the delineation of molecular mechanisms in bone growth and turnover in malignancy also fall within this program.
- Tumor Microenvironment and Therapeutic Resistance
Key areas include studying the effects of chemo- or radio-therapies on tumor and stromal cells and mechanism by which tumor stroma can confer therapeutic resistance.
Extracellular Matrix, Cell Adhesion Molecules and the Cytoskeleton and Nuclear Matrix
Key areas include research into the role of cytoskeletal proteins and the nuclear matrix in regulating gene expression, cellular proliferation, and apoptosis in the context of invasion, tumor progression and metastasis. The molecular characterization of cell-cell interactions and communication through gap-junctional structures, connexins, catenins, and cadherins is also included.
Key areas include research into the biology of angiogenesis, inducers and inhibitors of neovascularization, including growth factors; the development of technologies to identify novel factors that modulate angiogenesis are included. The program area also supports studies in the role of lymphangiogenesis in tumor progression and metastasis.
Glycoproteins and Tumor Metastasis
Key areas include the role of proteoglycans in metastasis; tumor glycoproteins and functional consequences of aberrant glycosylation on cell adhesion, tumor progression and metastasis.
Steroid Hormones and Cancer
Key areas include studies on nuclear receptor super-family: their role in modulating genomic and non-genomic effects; in cancer progression and metastasis; and in castration resistant cancers. (e.g., prostate and breast cancer); mechanisms of de novo or acquired resistance to hormone therapy; local production of steroid hormones by tumor and stromal cells; steroid receptor dependence of castration-resistant cancers; role of steroid hormones on stromal cells (e.g., endothelial and immune cells).