Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance

Alagundagi, Dhananjay B.; Ghate, Sudeep D.; Rajendra, Vinay Kumar J.; Gollapalli, Pavan; Shetty, Vijith; Dsouza, Caren; Shetty, Praveenkumar; Patil, Prakash

doi:10.1007/s13205-022-03422-w

Cited by 4 publications

(3 citation statements)

References 64 publications

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“…High ENO1 expression predicts poor prognosis in patients with liver cancer and lung cancer and also indicates more severe tumor type and later stage tumors ( Zhang, Lu & Yang, 2020 ; Zhang, Wang & Dong, 2018 ). Breast cancer lymphatic metastasis and ENO1 are also linked ( Alagundagi et al, 2023 ). ENO1 can increase the process of glycolysis, help prevent immune cell destruction and the role of growth inhibitors in tumors ( Hsiao et al, 2013 ), promote the growth of tumor blood vessels, provide more nutrients to cells, promote tumor growth and migration ( Huang et al, 2022a ), promote malignant proliferation, and act on tumor-related pathways ( Hua et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NMRAL2P promotes glycolysis and reduces ROS in head and neck tumors by interacting with the ENO1 protein and promoting GPX2 transcription

Nie,

Cao,

Yang

et al. 2023

PeerJ

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Background Metabolic reprogramming is a key marker in the occurrence and development of tumors. This process generates more reactive oxygen species (ROS), promoting the development of oxidative stress. To prevent ROS from harming tumor cells, tumor cells can increase the production of reducing agents to counteract excessive ROS. NMRAL2P has been shown to promote the production of reductive mRNA and plays an important role in the process of oxidative stress. Methods In this study, the clinical data and RNA sequencing of head and neck tumors were obtained from The Cancer Genome Atlas data set. The long non-coding RNA (LncRNA) related to oxidative stress were then identified using differential and correlation analyses. The differential expression and prognosis of the identified lncRNA were then verified using samples from the library of the Second Hospital of Hebei Medical University. Only NMRAL2P was substantially expressed in cancer tissues and predicted a poor prognosis. The tumor-promoting impact of NMRAL2P was then confirmed using in vitro functional assays. The data set was then split into high- and low-expression subgroups based on the median gene expression of NMRAL2P to obtain the mRNA that had a large difference between the two groups, and examine the mechanism of NMRAL2P on GPX2 using quantitative real-time PCR, RNA binding protein immunoprecipitation assay, and chromatin immunoprecipitation. Mass spectrometry was used to identify NMRAL2P-binding proteins and western blotting was used to investigate probable mechanisms. Results The lncRNA NMRAL2P is associated with oxidative stress in head and neck tumors. In vitro functional assays showed that the gene has a cancer-promoting effect, increasing lactic acid and superoxide dismutase production, and reducing the production of ROS and malondialdehyde. NMRAL2P promotes the transcription of GPX2 by binding to transcription factor Nrf2. The gene also inhibits the degradation of ENO1, a crucial enzyme in glycolysis, by binding to protein ENO1. Conclusions This study shows that NMRAL2P can promote glycolysis and reduce the harm to tumor cells caused by ROS. The gene can also be used as a possible target for the treatment of head and neck tumors.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NMRAL2P promotes glycolysis and reduces ROS in head and neck tumors by interacting with the ENO1 protein and promoting GPX2 transcription

Nie,

Cao,

Yang

et al. 2023

PeerJ

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“…In MCF-7 and MDA-MB-231 breast cancer cells, Hsp90 was involved in the stabilization and nuclear accumulation of E2F1 and E2F2, which may govern tumor progression [99]. In addition, a comprehensive bioinformatics analysis of breast cancer exosomes revealed Hsp90AA1 as a novel hub gene in the exosomal proteins derived from human breast cancer cells [100].…”

Section: Hsp90mentioning

confidence: 99%

Heat Shock Proteins and Breast Cancer

Zhang,

2024

IJMS

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Heat shock proteins (Hsps) are a group of stress-induced proteins involved in protein folding and maturation. Based on their molecular weight, Hsps can be divided into six families: small Hsps, Hsp40, Hsp60, Hsp70, Hsp90, and large Hsps. In the process of breast cancer tumorigenesis, Hsps play a central role in regulating cell reactions and functions including proliferation, metastasis, and apoptosis. Moreover, some of the critical Hsps also regulate the fine balance between the protective and destructive immunological responses within the tumor microenvironment. In this review, we systematically summarize the roles of major Hsps in breast cancer biology and point out the potential uses of these proteins in breast cancer diagnosis and therapy. Understanding the roles of different families of Hsps in breast cancer pathogenesis will help in the development of more effective prevention and treatment measures for breast cancer.

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“…⁠sEVs have been proposed as promising diagnostic biomarkers, therapeutic targets and drug delivery vehicles for breast [ 17 , 18 ]⁠ and other types of cancer [ 19 – 24 ].⁠ On the other hand, it has been shown that sEVs secreted by metastatic cells potentiate tumorigenic capacities of less aggressive neighbor recipient cells [ 8 , 9 , 13 , 15 , 16 , 25 – 36 ]⁠. Different studies have shown that sEVs secreted by metastatic BC cells potentiate tumorigenic and metastatic potential when incorporated into recipient cells [ 9 , 16 , 25 , 26 , 33 , 36 ]⁠.…”

Section: Introductionmentioning

confidence: 99%

Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities

Durán-Jara,

del Campo,

Gutiérrez

et al. 2024

Biol Res

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Background Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted glycoprotein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. Results We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV-MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. Conclusions As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.

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Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance

Cited by 4 publications

References 64 publications

Long non-coding RNA NMRAL2P promotes glycolysis and reduces ROS in head and neck tumors by interacting with the ENO1 protein and promoting GPX2 transcription

Long non-coding RNA NMRAL2P promotes glycolysis and reduces ROS in head and neck tumors by interacting with the ENO1 protein and promoting GPX2 transcription

Heat Shock Proteins and Breast Cancer

Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities

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