NEWS
HOW SOME CANCERS "Poison the Soil" TO BLOCK METASTASIS
Research shows therapeutic proteins could offer much needed treatment strategy for metastatic cancer
PRESS RELEASE
WEILL CORNELL STUDY SHOWS TRIPLE NEGATIVE BREAST CANCER METASTASIS CAN BE HALTED, POTENTIAL NEW THERAPIES ON HORIZON PRESS RELEASE
Researchers Reveal Aggressive Breast Cancer's Metastatic Path
CORNELL CENTER ON THE MICROENVIRONMENT AND METASTASIS AND NEUBERGER BERMAN LUNG CANCER RESEARCH CENTER PRESS RELEASE
Microenvironmental regulation of mesenchymal to epithelial transition promotes metastasis
Role of the lung microenvironment in de novo lung carcinogenesis, and in metastases derived from extrapulmonary neoplasms
Our research is focused around the lung as a central organ to study de novo lung carcinogenesis, as well as the initiation and progression of metastatic lesions derived from extrapulmonary neoplasms. The program integrates expertise in clinical and basic science to foster innovative research for the prevention, detection, and treatment of cancer. A major aim is to understand cancer cell intrinsic and extrinsic programs that regulate tumor growth and metastasis. Cancer cell intrinsic programs include aberrant signaling pathways, which are investigated at several levels including transcriptional regulation, epigenetic regulation, and regulation by small regulatory RNAs. Cancer cell extrinsic programs include the contribution of the tumor microenvironment; by dissecting the complexity of various stromal cell types that comprise the microenvironment we unravel heterotypic reciprocal signaling between the stromal cells and tumor epithelial compartments that contribute to tumor progression. We are interested in understanding how these two programs are integrated to regulate key tumorigenic processes including angiogenesis, inflammation, epithelial to mesenchymal transition, therapeutic resistance, metastasis initiation and progression. A major aim is to rapidly validate insights obtained from these investigations in preclinical and clinical settings, and to determine the diagnostic and therapeutic potential of candidate molecules in collaboration with clinicians.
Previously, we had demonstrated that recruited bone marrow-derived endothelial progenitor cells (EPCs) contribute to the angiogenic switch in primary tumor growth (Nolan et al. Genes and Dev. 2007, Ruzinova et al. Cancer Cell 2003), and in the progression of micrometastases to macrometastases (Gao et al. Science 2008). Furthermore, expression of either suicide genes (HSV-Tk) or shRNAs (such as VEGF-receptor 2 shRNA) in the bone marrow cells in vivo inhibited tumor angiogenesis and growth (Mellick et al. Cancer Research, 2010; Plummer et al. Cancer Research 2012, in review). More recently, we have shown that primary breast tumors generate premetastatic niches in the lung. These niches are predominantly comprised of recruited bone marrow-derived myeloid progenitor cells, express versican, which in a paracrine fashion, stimulate mesenchymal to epithelial transition (MET) of disseminated metastatic breast tumor cells to promote the formation of lethal metastases (Gao et al. Cancer Research 2012, also a review by Gao et al. Cancer Research, 2012, in press).
Previously, we had demonstrated that recruited bone marrow-derived endothelial progenitor cells (EPCs) contribute to the angiogenic switch in primary tumor growth (Nolan et al. Genes and Dev. 2007, Ruzinova et al. Cancer Cell 2003), and in the progression of micrometastases to macrometastases (Gao et al. Science 2008). Furthermore, expression of either suicide genes (HSV-Tk) or shRNAs (such as VEGF-receptor 2 shRNA) in the bone marrow cells in vivo inhibited tumor angiogenesis and growth (Mellick et al. Cancer Research, 2010; Plummer et al. Cancer Research 2012, in review). More recently, we have shown that primary breast tumors generate premetastatic niches in the lung. These niches are predominantly comprised of recruited bone marrow-derived myeloid progenitor cells, express versican, which in a paracrine fashion, stimulate mesenchymal to epithelial transition (MET) of disseminated metastatic breast tumor cells to promote the formation of lethal metastases (Gao et al. Cancer Research 2012, also a review by Gao et al. Cancer Research, 2012, in press).
An artists perspective of the tumor microenvironment
