Human breast tumor derived endothelial cells exhibit distinct biological properties

Hegde, Mangala; Bhat, Sevitha; Guruprasad, Kanive Parashiva; Moka, Rajasekhar; Ramachandra, Lingadakai; Satyamoorthy, Kapaettu; Joshi, Manjunath B.

doi:10.1111/boc.202100015

Cited by 5 publications

(2 citation statements)

References 58 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The heterogeneity of breast tumor-associated endothelial cell phenotypes across patients remains poorly inventoried at the single-cell level. TECs have significantly different biological characteristics compared with normal breast endothelial cells [ 37 ]. The heterogeneity of cancer cells is thought to be derived from clonal evolution.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing reveals small extracellular vesicles derived from malignant cells that contribute to angiogenesis in human breast cancers

Zhang,

Zhen,

Sun

et al. 2023

J Transl Med

View full text Add to dashboard Cite

Background Breast cancer is the most common cancer affecting women across the world. Tumor endothelial cells (TECs) and malignant cells are the major constituents of the tumor microenvironment (TME), but their origin and role in shaping disease initiation, progression, and treatment responses remain unclear due to significant heterogeneity. Methods Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed to investigate the presence of distinct cell subsets in the tumor microenvironment. InferCNV was used to identify cancer cells. Pseudotime trajectory analysis revealed the dynamic process of breast cancer angiogenesis. We validated the function of small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) in vitro experiments. Results We performed single-cell transcriptomics analysis of the factors associated with breast cancer angiogenesis and identified twelve subclusters of endothelial cells involved in the tumor microenvironment. We also identified the role of TECs in tumor angiogenesis and confirmed their participation in different stages of angiogenesis, including communication with other cell types via sEVs. Overall, the research uncovered the TECs heterogeneity and the expression levels of genes at different stages of tumor angiogenesis. Conclusions This study showed sEVs derived from breast cancer malignant cells promote blood vessel formation by activating endothelial cells through the transfer of PPP1R1B. This provides a new direction for the development of anti-angiogenic therapies for human breast cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing reveals small extracellular vesicles derived from malignant cells that contribute to angiogenesis in human breast cancers

Zhang,

Zhen,

Sun

et al. 2023

J Transl Med

View full text Add to dashboard Cite

show abstract

“…In addition, these vessels do not serve as normal barriers due to the lack of proper perivascular coverage and tight EC connections [242][243][244]. Not only that, the TECs that make up tumor blood vessels are also significantly different from normal endothelial cells (NECs), which are fragile, leaky, and highly proliferative and angiogenic [245]. Moreover, TECs are irregular in shape and size [237], and cells proliferate and migrate faster [229].…”

Section: Tumor Blood Vessels and Tumor-associated Endothelial Cellsmentioning

confidence: 99%

Stromal cells in the tumor microenvironment: accomplices of tumor progression?

Zhao,

Shen,

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), and cellular components include cancer cells and non-malignant cells such as immune cells and stromal cells. These three types of cells establish complex signals in the body and further influence tumor genesis, development, metastasis and participate in resistance to anti-tumor therapy. It has attracted scholars to study immune cells in TME due to the significant efficacy of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T (CAR-T) in solid tumors and hematologic tumors. After more than 10 years of efforts, the role of immune cells in TME and the strategy of treating tumors based on immune cells have developed rapidly. Moreover, ICI have been recommended by guidelines as first- or second-line treatment strategies in a variety of tumors. At the same time, stromal cells is another major class of cellular components in TME, which also play a very important role in tumor metabolism, growth, metastasis, immune evasion and treatment resistance. Stromal cells can be recruited from neighboring non-cancerous host stromal cells and can also be formed by transdifferentiation from stromal cells to stromal cells or from tumor cells to stromal cells. Moreover, they participate in tumor genesis, development and drug resistance by secreting various factors and exosomes, participating in tumor angiogenesis and tumor metabolism, regulating the immune response in TME and extracellular matrix. However, with the deepening understanding of stromal cells, people found that stromal cells not only have the effect of promoting tumor but also can inhibit tumor in some cases. In this review, we will introduce the origin of stromal cells in TME as well as the role and specific mechanism of stromal cells in tumorigenesis and tumor development and strategies for treatment of tumors based on stromal cells. We will focus on tumor-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated adipocytes (CAAs), tumor endothelial cells (TECs) and pericytes (PCs) in stromal cells.

show abstract