Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer

Dong, Menglu; Liu, Quan; Xu, Yi; Zhang, Qi

doi:10.3389/fcell.2022.842898

Cited by 17 publications

(14 citation statements)

References 82 publications

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“…Moreover, both breast cancer cells and MSC/ASC-derived EVs are essential for the crosstalk between MSCs/ASCs and breast cancer cells [ 63 , 67 , 68 ]. EVs are a heterogeneous group of membrane-bound vesicles released from cells by invagination and budding.…”

Section: Crosstalk Between Ascs and Breast Cancer Cellsmentioning

confidence: 99%

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Ritter

Kreis

Hoock

et al. 2022

Cancers

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Breast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Adipose tissue is the major microenvironment of breast cancer. Obesity changes the composition, structure, and function of adipose tissue, which is associated with inflammation and metabolic dysfunction. Interestingly, adipose tissue is rich in ASCs/MSCs, and obesity alters the properties and functions of these cells. As a key component of the mammary stroma, ASCs play essential roles in the breast cancer microenvironment. The crosstalk between ASCs and breast cancer cells is multilateral and can occur both directly through cell–cell contact and indirectly via the secretome released by ASC/MSC, which is considered to be the main effector of their supportive, angiogenic, and immunomodulatory functions. In this narrative review, we aim to address the impact of obesity on ASCs/MSCs, summarize the current knowledge regarding the potential pathological roles of ASCs/MSCs in the development of breast cancer, discuss related molecular mechanisms, underline the possible clinical significance, and highlight related research perspectives. In particular, we underscore the roles of ASCs/MSCs in breast cancer cell progression, including proliferation and survival, angiogenesis, migration and invasion, the epithelial–mesenchymal transition, cancer stem cell development, immune evasion, therapy resistance, and the potential impact of breast cancer cells on ASCS/MSCs by educating them to become cancer-associated fibroblasts. We conclude that ASCs/MSCs, especially obese ASCs/MSCs, may be key players in the breast cancer microenvironment. Targeting these cells may provide a new path of effective breast cancer treatment.

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Section: Crosstalk Between Ascs and Breast Cancer Cellsmentioning

confidence: 99%

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Ritter

Kreis

Hoock

et al. 2022

Cancers

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“…Recently, growing concentration has been laid on the extracellular vesicles, which are defined as nano-sized membrane-bound vesicles released by almost all cells under physiological and pathological processes ( 33 ). Referring to TNBC, extracellular vesicles were confirmed to deliver functional materials such as proteins, lipids, mRNAs, non-coding RNAs, and DNA fragments into extracellular location and thus play a significant role in shaping tumor microenvironment and in improving the capability of invasion and metastasis of TNBC ( 34 – 36 ). Our data confirmed higher vesicle-mediated transport activity in TNBC than ACC, which may contribute to elucidate the extreme difference in tumor aggressiveness and prognosis between TNBC and ACC.…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer

et al. 2022

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BackgroundAdenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC.MethodsWe applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information.ResultsA total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity.ConclusionThis study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.

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“…Recently, it was found that sEVs-derived proteins and nucleic acids components enter recipient cells through sEVs uptake pathway and enhanced recipient cells invasion and metastasis by affecting downstream signaling pathways and a series of cascade responses ( 96 ). It was shown that CAFs-derived sEVs carrying miR-181d-5p promoted BC cells invasion and migration by targeting cadal-related homeobox 2 (CDX2) and downregulating CDX2 and its downstream gene -homeobox ( 97 ).…”

Section: Sevs Derived From Breast Cancer and Their Role In Cancer Pro...mentioning

confidence: 99%

The role and application of small extracellular vesicles in breast cancer

Huang

et al. 2022

Front. Oncol.

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Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related deaths in women worldwide. Currently, patients’ survival remains a challenge in BC due to the lack of effective targeted therapies and the difficult condition of patients with higher aggressiveness, metastasis and drug resistance. Small extracellular vesicles (sEVs), which are nanoscale vesicles with lipid bilayer envelopes released by various cell types in physiological and pathological conditions, play an important role in biological information transfer between cells. There is growing evidence that BC cell-derived sEVs may contribute to the establishment of a favorable microenvironment that supports cancer cells proliferation, invasion and metastasis. Moreover, sEVs provide a versatile platform not only for the diagnosis but also as a delivery vehicle for drugs. This review provides an overview of current new developments regarding the involvement of sEVs in BC pathogenesis, including tumor proliferation, invasion, metastasis, immune evasion, and drug resistance. In addition, sEVs act as messenger carriers carrying a variety of biomolecules such as proteins, nucleic acids, lipids and metabolites, making them as potential liquid biopsy biomarkers for BC diagnosis and prognosis. We also described the clinical applications of BC derived sEVs associated MiRs in the diagnosis and treatment of BC along with ongoing clinical trials which will assist future scientific endeavors in a more organized direction.

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Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer

Cited by 17 publications

References 82 publications

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer

The role and application of small extracellular vesicles in breast cancer

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