Project description:We found that PC-3 cells consisted of rBC2LCN-positive and -negative subpopulations. To examine a global gene expression comparison between the rBC2LCN-positive and -negative subpopulations, DNA microarray was performed.
Project description:The application of compounds specifically targeting the cancer stem cells (CSCs), in addition to routinely used therapeutics, would likely improve the clinical outcome of head and neck squamous cell carcinoma (HNSCC). The previously described monoclonal antibody K984 (now found to recognize CD98) was used to identify, select and isolate a specific tumor subpopulation. These cells were molecularly characterized and subjected to serial transplantation experiments to determine the CSC properties. We show that CD98high cells, in contrast to CD98low cells, are able to generate tumors in immunodeficient mice and that the CD98high subpopulation expresses high levels of cell cycle control and DNA repair genes, while the CD98low fraction shows expression patterns that represent the more differentiated cells forming the bulk of the tumor. Transcriptional profiling of CD98high cells (n=4 fractions) of VU-SCC-OE xenograft tumors compared to CD98low cells (n=3 fractions) from the corresponding tumors.
Project description:The goal of this study was to identify signalling molecules downstream of CXCR4 in breast cancer cells. For this purpose, we sorted CXCR4-positive and CXCR4-negative cells from MDA-MB-231 breast cancer cell line by flow cytometry and performed microarrays analysis. Three sets of samples, each in quadruplicate, were analyzed. These include CXCR4-positive subpopulation, CXCR4-positive subpopulation treated with SDF-1 (ligand for CXCR4, also called CXCL12) for one hour and CXCR4-negative subpopulation.
Project description:The application of compounds specifically targeting the cancer stem cells (CSCs), in addition to routinely used therapeutics, would likely improve the clinical outcome of head and neck squamous cell carcinoma (HNSCC). The previously described monoclonal antibody K984 (now found to recognize CD98) was used to identify, select and isolate a specific tumor subpopulation. These cells were molecularly characterized and subjected to serial transplantation experiments to determine the CSC properties. We show that CD98high cells, in contrast to CD98low cells, are able to generate tumors in immunodeficient mice and that the CD98high subpopulation expresses high levels of cell cycle control and DNA repair genes, while the CD98low fraction shows expression patterns that represent the more differentiated cells forming the bulk of the tumor.
Project description:Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant pulmonary epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of unselected cells. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8-weeks post-selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short term assays and enhanced outgrowth of premalignant lesions in longer term assays, thus overcoming important aspects of “metastatic inefficiency.” Overall, our findings indicate that among premalignant pulmonary epithelial cells, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior.
Project description:As in other tumor types, progression of pancreatic cancer may require a functionally unique population of cancer stem cells. Although such cells have been identified in many invasive cancers, is not clear whether they emerge during early or late stages of tumorigenesis. Using mouse models and human pancreatic cancer cell lines, we investigated whether pre-invasive pancreatic neoplasia contains a subpopulation of cells with distinct morphologies and cancer stem cell like properties. Whole transcriptome anlaysis of AcTub Hi vs AcTub Low cells. Cells were labeled with an acetylated alpha tubulin antibody that recognized epitopes on the cell surface (AAT+). AcTub Hi vs Low cells were FACS sorted from the human pancreatic cancer cell lines CFPAC and AsPC1 CFPAC and AsPC1 cells were labeling with AcTub (acetylated alpha tubulin antibody) and then FACS sorted based on high or low levels of AcTub, and microarray analyses were run on biological replicates.
Project description:The brain microenvironment imposes a particularly intense selective pressure on metastasis initiating cells, but successful metastasis bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of this microenvironment, as they have been observed to confine brain metastasis without infiltrating the lesion. We describe a subpopulation of reactive astrocytes surrounding metastatic lesions that are characterized by the activation of STAT3 pathway. Blocking STAT3 signaling in this subpopulation of reactive astrocytes reduces experimental brain metastasis from different primary tumor sources, even at advanced stages of colonization. We conclude that brain metastatic cells induce and maintain the co-option of a pro-metastatic program driven by STAT3 in a subpopulation of reactive astrocytes. We also show that a safe and orally bioavailable treatment that inhibits STAT3 in patients with established brain metastasis and extracranial disease exhibits significant antitumor effects, especially in the CNS where several complete responses were achieved. Given that brain metastasis imposes significant morbidity and mortality, our experimental results suggest a novel treatment for increasing survival in patients with secondary brain tumors.