Project description:Glioblastoma multiforme (GBM) presents a formidable clinical challenge due to its complex microenvironment. Here, we introduce lipid droplet (LD)-loaded macrophages, or tumor-associated foam cells (TAFs), as a previously unidentified immune cell population in GBM. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we reveal that TAFs exhibit distinct pro-tumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis. Moreover, TAF presence correlates with worse patient outcome. Our mechanistic investigations demonstrate that TAF formation is facilitated by lipid cargo from extracellular vesicles released by GBM cells. Importantly, we demonstrate that targeting key enzymes involved in LD formation, such as DGAT1 or ACSL, effectively disrupts TAF functionality. This study establishes TAFs as a prominent immune cell entity in GBM and provides valuable insights into their interplay within the microenvironment. Disruptin
Project description:In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors. We used microarrays to evaluate transcriptional signature realted lipid droplet (LD)+ and LD- regions of patient glioblastoma (GBM) sections.
Project description:Experiment description to give context to the data set: Ductal carcinoma in situ (DCIS), the most common type of pre-invasive lesion of breast, is being detected with increasing frequency with the advent of mammographic screening. Surgery is the mainstay for the treatment of DCIS. Based on the clinic-pathological features of DCIS, this may be followed by radiotherapy and/or endocrine therapy. The qualitative assessment of histological grade, expression of single protein biomarkers and more recently, mRNA analysis (DCIS Score) have been used to make these decisions. However, these factors do not fully predict the likelihood of development of invasive breast cancer treated with breast-conserving surgery. A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of development of invasive breast cancer. Using Human Clariom D Pico Assay, we aim to compare the transcriptome profiles of DCIS in relation to development of invasive breast cancer (INV-BC) versus Non-INV-BC cases. Experimental Methods Clariom D Pico Human Transcriptome Array were performed according to Applied Biosystems/Thermo Fisher Scientific’s instructions. Experimental protocols are summarized in detail in Supplementary Methods (Supplementary Data). Sample annotation We compared the relative gene expression in development of invasive breast cancer (INV-BC) versus Non-INV-BC cases in Singapore cohort-59 cases (discovery cohort) and Italian cohort-50 cases (validation cohort). Microplate Plate and Well IDs are also provided as Clariom D ID list per cohort. Author information Dr. Sunil Badve is the Principal Investigator. Raw Data Probe Cell Intensity (CELL) and .ARR files which contain the design information for this study are provided (Human Clariom D Pico Assay).
Project description:In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors. We used microarrays to evaluate transcriptional signature realted to 3D (LD⁺) cultures compared to 2D (LD⁻) cultures from primary glioblastoma (GBM) cell line.
Project description:In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors. We used microarrays to evaluate transcriptional signature of adaptation to acidosis (pH 6.4) in PANC1 pancreatic cancer cells.