Sphingomyelins secreted by mammosphere-derived cells present a novel mechanism for the low mammary cancer incidence observed in certain mammals
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE145536 | GEO | 2020/12/01
REPOSITORIES: GEO
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Project description:Determining mechanisms that naturally protect species from developing cancer is critical in order to prevent and treat cancer. Here, we describe a novel cancer-suppressing mechanism, via the secretion of bioactive factors by mammary cells, that is present in domesticated mammals with a low mammary cancer incidence. Specifically, these bioactive factors induced triple-negative breast cancer cell (TNBC) death in vitro and reduced tumorigenicity in a xenograft TNBC mouse model in vivo. RNA deep sequencing showed significant downregulation of genes associated with breast cancer progression in secretome-cultured TNBC cells. Further in-depth multi-omics analysis identified sphingomyelins as key secreted factors, and their role was confirmed via inhibition of the sphingomyelin signaling pathway. We speculate that secreted sphingomyelins in the mammary gland of mammals with a naturally low incidence of mammary cancer mediate the elimination of cancer cells. This study contributes to the growing list of protective mechanisms identified in cancer-proof species.
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Project description:Sphingomyelins secreted by mammosphere-derived cells present a novel mechanism for the low mammary cancer incidence observed in certain mammals
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Project description:Comparison of different culture conditions of the human breast cancer cell line SUM149. We cultured the cells adherent in standard medium in normal cell culture flasks and as mammospheres in MammoCult (stemcell technologies) in ultra low-attachment flasks
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Project description:MicroRNAs are likely to play pivotal roles in both stem cells and cancer, and are further promising candidates for future therapeutic purposes. To understand the role of miR206 in mammary cell differentiation, we profiled the transcription of mamary stem-like cells, comparing control HC11 cells (unspecific miRNA mimic treated) with HC11 cells transfected with miRNA-206 mimic.
2019-05-15 | GSE76251 | GEO
Project description:We report the role of AIB1D4 in early stage breast cancer progression. Using CRISPR editing, we generated isogeneic cell lines that only express AIB1D4 and not full length AIB1 then extracted RNA for sequencing from cell lines and mamary fat pad xenografts in SCID/Beige mice. Data was aligned to Hg19 with STAR and processed with EdgeR.
2020-11-08 | GSE139270 | GEO
Project description:Mammalian milk is not only a source of nutrition for the newborn, but also contains various components that regulate further development. For instance, milk is an abundant source of microRNAs (miRNAs), which are evolutionary conserved small non-coding RNAs that are involved in post-transcriptional regulation of target mRNA. MiRNAs present in milk can occur in extracellular vesicles (EV), which are nanosized membrane vesicles released by many cell types as a means of intercellular communication. The membrane of EV protects enclosed miRNAs from degradation and harbors molecules that allow specific targeting to recipient cells. Although several studies have investigated the miRNA content in milk EV from individual species, little is known about the evolutionary conserved nature of EV-associated miRNAs among different species. In this study, we profiled the miRNA content of purified EV from human and porcine milk. These data were compared to published studies on EV from human, cow, porcine and panda milk to assess the overlap in the top 20 most abundant miRNAs. Interestingly, several abundant miRNAs were shared between species (e.g. let-7 family members let-7a, let-7b, let-7f, and miR-148a). Moreover, these miRNAs have been implicated in immune-related functions and regulation of cell growth and signal transduction. The conservation of these miRNA among species, not only in their sequence homology , but also in their incorporation in milk EV of several species, suggests that they are evolutionarily selected to regulate cell function in the newborn.
2018-08-11 | GSE118409 | GEO
Project description:BackgroundThe aetiology of Africa's easterly-lying corridor of squamous cell oesophageal cancer is poorly understood. Micronutrient deficiencies have been implicated in this cancer in other areas of the world, but their role in Africa is unclear. Without prospective cohorts, timely insights can instead be gained through ecological studies.MethodsAcross Africa we assessed associations between a country's oesophageal cancer incidence rate and food balance sheet-derived estimates of mean national dietary supplies of 7 nutrients: calcium (Ca), copper (Cu), iron (Fe), iodine (I), magnesium (Mg), selenium (Se) and zinc (Zn). We included 32 countries which had estimates of dietary nutrient supplies and of better-quality GLOBCAN 2012 cancer incidence rates. Bayesian hierarchical Poisson lognormal models were used to estimate incidence rate ratios for oesophageal cancer associated with each nutrient, adjusted for age, gender, energy intake, phytate, smoking and alcohol consumption, as well as their 95% posterior credible intervals (CI). Adult dietary deficiencies were quantified using an estimated average requirements (EAR) cut-point approach.ResultsAdjusted incidence rate ratios for oesophageal cancer associated with a doubling of mean nutrient supply were: for Fe 0.49 (95% CI: 0.29-0.82); Mg 0.58 (0.31-1.08); Se 0.40 (0.18-0.90); and Zn 0.29 (0.11-0.74). There were no associations with Ca, Cu and I. Mean national nutrient supplies exceeded adult EARs for Mg and Fe in most countries. For Se, mean supplies were less than EARs (both sexes) in 7 of the 10 highest oesophageal cancer ranking countries, compared to 23% of remaining countries. For Zn, mean supplies were less than the male EARs in 8 of these 10 highest ranking countries compared to in 36% of other countries.ConclusionsEcological associations are consistent with the potential role of Se and/or Zn deficiencies in squamous cell oesophageal cancer in Africa. Individual-level analytical studies are needed to elucidate their causal role in this setting.
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Project description:Mammalian milk is not only a source of nutrition for the newborn, but also contains various components that regulate further development. For instance, milk is an abundant source of microRNAs (miRNAs), which are evolutionary conserved small non-coding RNAs that are involved in post-transcriptional regulation of target mRNA. MiRNAs present in milk can occur in extracellular vesicles (EVs), which are nanosized membrane vesicles released by many cell types as a means of intercellular communication. The membrane of EVs protects enclosed miRNAs from degradation and harbors molecules that allow specific targeting to recipient cells. Although several studies have investigated the miRNA content in milk EVs from individual species, little is known about the evolutionary conserved nature of EV-associated miRNAs among different species. In this study, we profiled the miRNA content of purified EVs from human and porcine milk. These data were compared to published studies on EVs from human, cow, porcine, and panda milk to assess the overlap in the top 20 most abundant miRNAs. Interestingly, several abundant miRNAs were shared between species (e.g., let-7 family members let-7a, let-7b, let-7f, and miR-148a). Moreover, these miRNAs have been implicated in immune-related functions and regulation of cell growth and signal transduction. The conservation of these miRNA among species, not only in their sequence homology, but also in their incorporation in milk EVs of several species, suggests that they are evolutionarily selected to regulate cell function in the newborn.
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Project description:Mammosphere medium (Grange et al. Neoplasia 2008;10(12):1433-43) contains epidermal growth factor (EGF), insulin and basic fibroblast growth factor (bFGF) that may influence transcript expression in a way not necessarily related to the assembly of mammspheres. To identify the set of genes associated mammosphere cell growth medium we analyzed two prototypic situations in triplicate experiments: TUBO cells (a mouse breast cancer cell line derived by Balb-neuT mice) grown in DMEM under adherent conditions (TDA), TUBO cells grown in Mammosphere medium under adherent conditions (TMA).
2013-11-30 | GSE26517 | GEO
Project description:Mammosphere medium (Grange et al. Neoplasia 2008;10(12):1433-43) contains epidermal growth factor (EGF), insulin and basic fibroblast growth factor (bFGF) that may influence transcript expression in a way not necessarily related to the assembly of mammspheres. To identify the set of genes associated mammosphere cell growth medium we analyzed two prototypic situations in triplicate experiments: TUBO cells (a mouse breast cancer cell line derived by Balb-neuT mice) grown in DMEM under adherent conditions (TDA), TUBO cells grown in Mammosphere medium under adherent conditions (TMA). Two prototypic situations in triplicate experiments were analysed: TUBO cells (Rovero et al. Gene Ther 2001;8(6):447-52) grown in DMEM under adherent conditions (TDA), TUBO cells grown in Mammosphere medium under adherent conditions (TMA).
2013-11-30 | E-GEOD-26517 | biostudies-arrayexpress