Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distinct tumor architectures for metastatic colonization of the brain [Flura-seq]

ABSTRACT: Brain metastasis is a dismal complication of cancer that hinges on the initial survival and outgrowth of disseminated cancer cells. To better understand these crucial early stages of brain metastatic colonization, we investigated two prevalent sources of cerebral relapse in the clinic, triple-negative breast cancer (TNBC) and HER2+ breast cancer (HER2BC). We elucidated distinctive early tumor architectures, physical and functional stromal interfaces, and autocrine growth programs employed by these two tumor types to colonize the brain. TNBC cells form extensive perivascular sheath colonies with diffusive contact with astrocytes and microglia. In striking contrast, heightened autonomous deposition of several extracellular matrix components prompts HER2BC cells to colonize the brain as compact, spheroidal colonies, segregating stromal cells to the periphery of the colony. Single-cell dissection of the spatially resolved tumor microenvironment (TME) reveals that brain metastases activate – to different degrees – the canonical stages of the disease-associated microglia (DAM) response previously defined in Alzheimer’s disease. Differential engagement of paracrine tumor-DAM signaling through the receptor AXL suggests specific pro-metastatic functions of the tumor architecture in both TNBC perivascular and HER2BC spheroidal colonies. Collectively, our findings illuminate the distinct stereospatial features of two different yet highly efficient modes of brain colonization, and the relevance of these features in future efforts to leverage the TME to treat brain metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223247 | GEO | 2023/05/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Distinct tumor architectures for metastatic colonization of the brain [scRNA-seq]

Project description:Brain metastasis is a dismal complication of cancer that hinges on the initial survival and outgrowth of disseminated cancer cells. To better understand these crucial early stages of brain metastatic colonization, we investigated two prevalent sources of cerebral relapse in the clinic, triple-negative breast cancer (TNBC) and HER2+ breast cancer (HER2BC). We elucidated distinctive early tumor architectures, physical and functional stromal interfaces, and autocrine growth programs employed by these two tumor types to colonize the brain. TNBC cells form extensive perivascular sheath colonies with diffusive contact with astrocytes and microglia. In striking contrast, heightened autonomous deposition of several extracellular matrix components prompts HER2BC cells to colonize the brain as compact, spheroidal colonies, segregating stromal cells to the periphery of the colony. Single-cell dissection of the spatially resolved tumor microenvironment (TME) reveals that brain metastases activate – to different degrees – the canonical stages of the disease-associated microglia (DAM) response previously defined in Alzheimer’s disease. Differential engagement of paracrine tumor-DAM signaling through the receptor AXL suggests specific pro-metastatic functions of the tumor architecture in both TNBC perivascular and HER2BC spheroidal colonies. Collectively, our findings illuminate the distinct stereospatial features of two different yet highly efficient modes of brain colonization, and the relevance of these features in future efforts to leverage the TME to treat brain metastasis.

2023-05-02 | GSE223309 | GEO

Distinct tumor architectures for metastatic colonization of the brain [RNA-seq]

2023-05-02 | GSE223351 | GEO

PTEN-restoration abrogates brain colonization and perivascular niche invasion by melanoma cells

Project description:Background: Melanoma brain metastases (MBM) continues to be a significant clinical problem with limited treatment options. Highly invasive melanoma cells migrate along the vasculature and perivascular cells may contribute to residual disease and recurrence. PTEN loss and hyperactivation of AKT occur in MBM; however, a role for PTEN/AKT in perivascular invasion has not been described. Methods: We used in vivo intracranial injections of murine melanoma and bulk RNA sequencing of melanoma cells co-cultured with brain endothelial cells (brECs) to investigate brain colonization and perivascular invasion. Results: We found that PTEN-null melanoma cells were highly efficient at colonizing the perivascular niche relative to PTEN-expressing counterparts. PTEN re-expression (PTEN-RE) in melanoma significantly reduced brain colonization and migration along the vasculature. We hypothesized this phenotype was mediated through vascular-induced TGFβ secretion, which drives AKT phosphorylation. Disabling TGFβ signaling in melanoma cells reduced colonization and perivascular invasion; however, introduction of constitutively-active myristolated-AKT (myrAKT) restored overall tumor size but not perivascular invasion. Conclusions: PTEN loss facilitates perivascular brain colonization and invasion of melanoma. TGFβ-AKT signaling partially contributes to this phenotype, but further studies are needed to determine the complementary mechanisms that enable melanoma cells to both survive and spread along the brain vasculature.

2023-12-26 | GSE247232 | GEO

Development of an immune-related prognostic biomarker for triple-negative breast cancer

Project description:Triple-negative breast cancer represents approximately 15–20% of all reported breast cancer cases, and is characterized by a shorter survival time and higher mortality rates compared to other breast cancer sub-types. Tumor microenvironment (TME) refers to the internal and external environment of tumor tissue. Increasing evidence indicates that a tumor’s microenvironment is tightly associated with the immunological surveillance and defense during the development of breast cancer. Although oncology studies employing digital dissection methodologies have provided some insight on the biological features of TME, the development of methods to investigate the cellular composition of the tumor microenvironment remain an important research priority. In this study, we extracted whole transcriptome from 30 Triple-negative breast cancer (TNBC) patients and then used bioinformatics approaches to characterize cell type content in tumor tissue compared with para-cancerous tissue. We identified 4 types of enriched immune cells and 6 types of downregulated immune cells in the tumor tissue samples. After comprehensive bioinformatics analyses, we developed an ‘immune infiltration score’ (IIS) to quantitatively model immune cell infiltration in TNBC. To demonstrate the utility of the IIS, we used 2 independent datasets for validation. We found that patients with a higher IIS showing a longer progression-free survival time and significantly better prognosis than those with a lower IIS value. In sum, we explored the immune infiltration landscape in 30 TNBC patients and provided a novel and reliable biomarker IIS to evaluate the progression-free survival and prognosis in the TNBC patients.

2021-10-18 | E-MTAB-10886 | biostudies-arrayexpress

Targeting tumor-stromal interactions in triple negative breast cancer using a human vascularized micro-tumor model

Project description:Background: Triple-negative breast cancer (TNBC) is characterized by its highly aggressive pathology and limited number of approved targeted therapies. Emerging evidence suggests that stromal cells within the tumor microenvironment (TME) play a crucial role in TNBC progression, making them potential therapeutic targets. Yet the molecular basis of stromal cell activation and tumor-stromal crosstalk in TNBC is poorly understood, limiting the development of therapies targeted to this axis. Methods: To explore potential therapeutic targets within the stromal niche of TNBC, we employed an advanced human in vitro microphysiological system model – the vascularized microtumor (VMT) – in which perfused vascular networks within a microfluidic platform self-assemble in a complex extracellular matrix (ECM) and supply nutrients and drugs to growing tumors. By leveraging single-cell RNA sequencing (scRNA-seq), we investigated gene expression patterns, cellular heterogeneity, and intercellular communication within TNBCs. Results: Our analysis revealed that histopathologically-normal human breast tissue-derived stromal cells activate neoplastic signaling pathways when exposed to the TNBC TME. Through a comparison of these interactions in VMTs with scRNA-seq data obtained from clinical specimens, we successfully identified therapeutic targets situated at the tumor-stromal interface that hold potential clinical significance. Promising results were observed in TNBC VMTs when combining treatments that target Tie2 signaling, thereby normalizing vasculature, with tumor-targeted paclitaxel. Furthermore, dual inhibition of Her3 and Akt also demonstrated efficacy against TNBC. Conclusions: By using an organotypic in vitro VMT model to recapitulate key components of the TNBC TME, we demonstrate the potential of inducing a favorable tumor microenvironment as a targeted therapeutic approach in TNBC.

2024-01-05 | GSE238090 | GEO

Project description:PTEN-restoration abrogates brain colonization and perivascular invasion by melanoma cells

| PRJNA1032415 | ENA

Gene expressions in pancreatic cancer cells

Project description:We used time-dependent spheroidal cultures of pancreatic cancer cells to investigate how spatiotemporal regulation in spheroids induces epithelial-mesenchymal plasticity (EMP). We generated a round bottom spheroidal model using M-NM-23 integrin-negative pancreatic cancer cells in 2D conventional monolayer cultures, and compared the expression of integrin signaling-related genes that induce spheroidal geometry to determine if spheroidal geometry induces integrin switching. To identify the potential genes whose expression changed in response to culture conditions, we performed microarray analysis of gene expression in human MIA PaCa-2 cells grown under monolayer and spheroid culture conditions for 6 days and 13 days.

2014-08-06 | E-GEOD-60139 | biostudies-arrayexpress

Neural activity recorded in breast tumors originates from the sympathetic nervous

Project description:The autonomic nervous system (ANS) is a regulator of major pathological events in the tumor microenvironment (TME) of solid carcinomas where the branches of ANS have antagonistic effects on tumor growth and metastasis. Neural activity recorded from breast tumors may be associated with autonomic system function. To test this hypothesis, we performed in vivo chronic electrical recordings from murine mammary tumors of triple negative breast cancers (TNBC) following complete sub-diaphragmatic vagotomy and chemical sympathectomy. In addition to TNBC mammary tumors, we also obtained daily electrical recordings from mammary tumors overexpressing human epidermal growth factor receptor-2 (HER2) following chemical sympathectomy. Our results show that tumoral neural activity is partially blocked in vagotomized animals while it is completely absent in the sympathectomized subjects. These studies indicate that neural activity in TNBC and HER2+ tumors is predominantly generated by peripheral nor-adrenergic sympathetic nerves and provide evidence of a strong active link between the brain and tumor through the autonomic nervous system. The results implicate a new and as yet unexplored mechanism to investigate the potential role of the sympathetic nervous system in the regulation of tumor growth and metastasis.

2024-02-05 | GSE254740 | GEO

Responsiveness of hypomethylated and control tumor cells to canonical Wnt-signalling

Project description:During metastasis, cancer cells travel the circulation to colonize distant sites. Due to the rarity of these events, the immediate cell fate decisions of metastasizing tumor cells (mTC) are poorly understood and the role of the endothelium, as dissemination interface, remains elusive. Using a novel combinatorial mTC enrichment approach, we provide a first transcriptional blueprint of the early colonization process

2023-10-02 | GSE232855 | GEO

Gene chip (Clariom S) analysis of 12 corresponding pairs of TECs and NECs from human colorectal carcinoma patients from different prognostic TMEs (Th1-TME vs Control-TME)

Project description:Tumor endothelial cells (TECs) and corresponding normal endothelial cells (NECs) were isolated from 12 different human colocrectal carcinoma (CRC) patients with different prognostic tumor microenvironments (TME: Th1-TME vs Control-TME).

2023-05-01 | E-MTAB-10465 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data