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Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer.

ABSTRACT: Breast cancer is one of the most-common female malignancies with a high risk of relapse and distant metastasis. The distant metastasis of breast cancer exhibits organotropism, including brain, lung, liver and bone. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells with tumor-initiating ability, which participate in regulating distant metastasis in breast cancer. We investigated the heterogeneity of BCSCs according to biomarker status, epithelial or mesenchymal status and other factors. Based on the classical "seed and soil" theory, we explored the effect of BCSCs on the metastatic organotropism in breast cancer at both "seed" and "soil" levels, with BCSCs as the "seed" and BCSCs-related microenvironment as the "soil". We also summarized current clinical trials, which assessed the safety and efficacy of BCSCs-related therapies. Understanding the role of BCSCs heterogeneity for regulating metastatic organotropism in breast cancer would provide a new insight for the diagnosis and treatment of advanced metastatic breast cancer.

SUBMITTER: Wang C

PROVIDER: S-EPMC8605572 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer.

Wang Cenzhu C Xu Kun K Wang Runtian R Han Xin X Tang Jinhai J Guan Xiaoxiang X Guan Xiaoxiang X

Journal of experimental & clinical cancer research : CR 20211120 1

Breast cancer is one of the most-common female malignancies with a high risk of relapse and distant metastasis. The distant metastasis of breast cancer exhibits organotropism, including brain, lung, liver and bone. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells with tumor-initiating ability, which participate in regulating distant metastasis in breast cancer. We investigated the heterogeneity of BCSCs according to biomarker status, epithelial or mesenchymal status ...[more]

PMID: 34801088

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Project description:BackgroundCancer metastasis is a complex process involving the spread of malignant cells from a primary tumor to distal organs. Understanding this cascade at a mechanistic level could provide critical new insights into the disease and potentially reveal new avenues for treatment. Transcriptome profiling of spontaneous cancer models is an attractive method to examine the dynamic changes accompanying tumor cell spread. However, such studies are complicated by the underlying heterogeneity of the cell types involved. The purpose of this study was to examine the transcriptomes of metastatic breast cancer cells using the well-established MMTV-PyMT mouse model.MethodsOrgan-derived metastatic cell lines were harvested from 10 female MMTV-PyMT mice. Cancer cells were isolated and sorted based on the expression of CD44low/EpCAMhigh or CD44high/EpCAMhigh surface markers. RNA from each cell line was extracted and sequenced using the NextSeq 500 Illumina platform. Tissue-specific genes were compared across the different metastatic and primary tumor samples. Reads were mapped to the mouse genome using STAR, and gene expression was quantified using RSEM. Single-cell RNA-seq (scRNA-seq) was performed on select samples using the ddSeq platform by BioRad and analyzed using Seurat v3.2.3. Monocle2 was used to infer pseudo-time progression.ResultsComparison of RNA sequencing data across all cell populations produced distinct gene clusters. Differential gene expression patterns related to CD44 expression, organ tropism, and immunomodulatory signatures were observed. scRNA-seq identified expression profiles based on tissue-dependent niches and clonal heterogeneity. These cohorts of data were narrowed down to identify subsets of genes with high expression and known metastatic propensity. Dot plot analyses further revealed clusters expressing cancer stem cell and cancer dormancy markers. Changes in relevant genes were investigated across pseudo-time and tissue origin using Monocle2. These data revealed transcriptomes that may contribute to sub-clonal evolution and treatment evasion during cancer progression.ConclusionsWe performed a comprehensive transcriptome analysis of tumor heterogeneity and organ tropism during breast cancer metastasis. These data add to our understanding of metastatic progression and highlight targets for breast cancer treatment. These markers could also be used to image the impact of tumor heterogeneity on metastases.

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Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer.

Publications

Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer.

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