Transcriptomics

Dataset Information

0

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


ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE238090 | GEO | 2024/01/05

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-07-07 | GSE234832 | GEO
2019-10-31 | E-MTAB-8483 | biostudies-arrayexpress
2015-05-13 | GSE68795 | GEO
2013-06-01 | E-GEOD-36693 | biostudies-arrayexpress
2023-08-22 | GSE212890 | GEO
2023-06-10 | GSE234129 | GEO
2022-10-13 | PXD034154 | Pride
2023-09-27 | E-MTAB-13300 | biostudies-arrayexpress
2021-02-28 | GSE162301 | GEO
2021-02-28 | GSE165211 | GEO