Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Estrogen receptor positive (ER+) breast cancer (BC) represents a significant proportion of BC brain metastasis (BCBM) but remains understudied. Here, we report that FGFR1-amplification, a well-established driver of ER+ BC endocrine resistance, promotes ER+ BCBM colonization in young and aged mice, through brain-dependent mechanisms. FGFR1-dependent brain colonization in young and aged mice occurs via canonical FGF2/FGFR1 signaling and non-canonical NCAM1/FGFR1 interactions. Astrocytic FGF2-mediated paracrine activation of FGFR1 promoted BCBMs in estrogen36 treated young mice, but FGF2 signaling decreased in the brain with aging and estrogen-depletion. Neuronal and glial NCAM1, which remain unchanged in young and aged brains, promoted adhesion to neurons and migration of ER+ BC cells, suggesting that interactions with astrocytes and neurons facilitate early ER+ BCBM colonization through FGFR1. Importantly, FDA-approved FGFR inhibitors effectively blocked early but not late metastatic progression only in young mice, suggesting limited efficacy of FGFR inhibitors to block non-kinase-dependent FGFR1 functions in vivo.
Project description:Estrogen receptor positive (ER+) breast cancer (BC) represents a significant proportion of BC brain metastasis (BCBM) but remains understudied. Here, we report that FGFR1-amplification, a well-established driver of ER+ BC endocrine resistance, promotes ER+ BCBM colonization in young and aged mice, through brain-dependent mechanisms. FGFR1-dependent brain colonization in young and aged mice occurs via canonical FGF2/FGFR1 signaling and non-canonical NCAM1/FGFR1 interactions. Astrocytic FGF2-mediated paracrine activation of FGFR1 promoted BCBMs in estrogen36 treated young mice, but FGF2 signaling decreased in the brain with aging and estrogen-depletion. Neuronal and glial NCAM1, which remain unchanged in young and aged brains, promoted adhesion to neurons and migration of ER+ BC cells, suggesting that interactions with astrocytes and neurons facilitate early ER+ BCBM colonization through FGFR1. Importantly, FDA-approved FGFR inhibitors effectively blocked early but not late metastatic progression only in young mice, suggesting limited efficacy of FGFR inhibitors to block non-kinase-dependent FGFR1 functions in vivo.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression. Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.
Project description:The objective of this study was to determine the extent to which paracrine action of 17-beta-estradiol on ER+ mouse astrocytes, affect gene expression of MDA231-derived brain trophic 231BR cells. Microarray analysis was performed in triplicate samples from 231BR cells treated with vehicle (OH), 10nM Estradiol (E2), alone or in combination with mouse astrocytes. 231BR-EGFP cells were sorted after 24h co-culture.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs. Two-condition experiment, KP MSCs vs. 3A6 MSCs.