Dataset Information

Unveiling functional heterogeneity in breast cancer multicellular tumor spheroids through single-cell RNA-seq.

ABSTRACT: Heterogeneity is an intrinsic characteristic of cancer. Even in isogenic tumors, cell populations exhibit differential cellular programs that overall supply malignancy and decrease treatment efficiency. In this study, we investigated the functional relationship among cell subtypes and how this interdependency can promote tumor development in a cancer cell line. To do so, we performed single-cell RNA-seq of MCF7 Multicellular Tumor Spheroids as a tumor model. Analysis of single-cell transcriptomes at two-time points of the spheroid growth, allowed us to dissect their functional relationship. As a result, three major robust cellular clusters, with a non-redundant complementary composition, were found. Meanwhile, one cluster promotes proliferation, others mainly activate mechanisms to invade other tissues and serve as a reservoir population conserved over time. Our results provide evidence to see cancer as a systemic unit that has cell populations with task stratification with the ultimate goal of preserving the hallmarks in tumors.

SUBMITTER: Mucino-Olmos EA

PROVIDER: S-EPMC7391783 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Unveiling functional heterogeneity in breast cancer multicellular tumor spheroids through single-cell RNA-seq.

Muciño-Olmos Erick Andrés EA Vázquez-Jiménez Aarón A Avila-Ponce de León Ugo U Matadamas-Guzman Meztli M Maldonado Vilma V López-Santaella Tayde T Hernández-Hernández Abrahan A Resendis-Antonio Osbaldo O

Scientific reports 20200729 1

Heterogeneity is an intrinsic characteristic of cancer. Even in isogenic tumors, cell populations exhibit differential cellular programs that overall supply malignancy and decrease treatment efficiency. In this study, we investigated the functional relationship among cell subtypes and how this interdependency can promote tumor development in a cancer cell line. To do so, we performed single-cell RNA-seq of MCF7 Multicellular Tumor Spheroids as a tumor model. Analysis of single-cell transcriptome ...[more]

PMID: 32728097

Similar Datasets

Project description:BackgroundBreast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets.MethodsBioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes.ResultsThe analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells.ConclusionThis study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Dataset Information

Unveiling functional heterogeneity in breast cancer multicellular tumor spheroids through single-cell RNA-seq.

Publications

Unveiling functional heterogeneity in breast cancer multicellular tumor spheroids through single-cell RNA-seq.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets