Pulmonary <i>Staphylococcus aureus</i> infection regulates breast cancer cell metastasis via neutrophil extracellular traps (NETs) formation

Qi, Jialong; He, Ju-Liang; Liu, Cun-Bao; Jin, Sun; Gao, Ruiyu; Xu, Yang; Bai, Hongmei; Ma, Yanbing

doi:10.1002/mco2.22

Cited by 17 publications

(8 citation statements)

References 41 publications

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“…This study suggested that expression of some key radiation signature genes appear to be altered by such infections. We also suggest that neutrophil extracellular traps (or NETs; Qi et al 2020) may activate biochemical pathways that are present in early radiation responses. An early step in the formation of these structures is chromosome decondensation followed by the fragmentation of DNA which act as extracellular fibers which bind pathogens (such as S. aureus) in a process similar to autophagy in neutrophils (NETosis).…”

Section: Discussionmentioning

confidence: 90%

Improved radiation expression profiling in blood by sequential application of sensitive and specific gene signatures

Mucaki

Shirley

Rogan

2021

Preprint

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Purpose: Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap some viral infections. We recently showed that these human radiation signatures produced unexpected false positive misclassification of Influenza and Dengue infected samples. The present study investigates these and other confounders, and then mitigates their effects on signature accuracy. Methods: This study investigated recall by previous and novel radiation signatures independently derived from multiple Gene Expression Omnibus datasets on common and rare non-malignant blood disorders and blood-borne infections (thromboembolism, S. aureus bacteremia, malaria, sickle cell disease, polycythemia vera, and aplastic anemia). Normalized expression levels of signature genes are used as input to machine learning-based classifiers to predict radiation exposure in other hematological conditions. Results: Except for aplastic anemia, these blood-borne disorders modify the normal baseline expression values of genes present in radiation signatures, leading to false-positive misclassification of radiation exposures in 8 to 54% of individuals. Shared changes, predominantly in DNA damage response and apoptosis-related gene transcripts in radiation and confounding hematological conditions, compromise the utility of these signatures for radiation assessment. These confounding conditions (sickle cell disease, thromboembolism, S. aureus bacteremia, malaria) induce neutrophil extracellular traps, initiated by chromatin decondensation, DNA damage response and fragmentation followed by programmed cell death. Riboviral infections (for example, Influenza, Dengue fever) are proposed to deplete RNA binding proteins, inducing R-loops in chromatin which collide with replication forks resulting in DNA damage, and apoptosis. To mitigate the effects of confounders, we evaluated predicted radiation positive samples with novel gene expression signatures derived from radiation-responsive transcripts encoding secreted blood plasma proteins whose expression levels are unperturbed by these conditions. Conclusions: This approach identifies and eliminates misclassified samples with underlying hematological or infectious conditions, leaving only samples with true radiation exposures. Diagnostic accuracy is significantly improved by selecting genes that maximize both sensitivity and specificity in the appropriate tissue using combinations of the best signatures for each of these classes of signatures.

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Section: Discussionmentioning

confidence: 90%

Improved radiation expression profiling in blood by sequential application of sensitive and specific gene signatures

Mucaki

Shirley

Rogan

2021

Preprint

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“…The levels of plasma NETs in patients with lung cancer, cervical cancer, and pancreatic cancer are significantly higher than those in healthy controls and are related to tumor recurrence and metastasis. 194 In tumor metastasis, NETs are mainly involved in the spread of cancer cells and awakening dormant tumor cells. NETs can induce EMT of primary tumor cells in the early stage of metastasis and lead to the activation of inflammatory signaling pathways such as NF‐kB and STAT3, thereby enhancing the mobility and invasiveness of cancer cells and promoting metastatic growth.…”

Section: Components and Mechanisms Involved In Metastasismentioning

confidence: 99%

Tumor metastasis: Mechanistic insights and therapeutic interventions

Liu

Yang

et al. 2021

MedComm

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Cancer metastasis is responsible for the vast majority of cancer‐related deaths worldwide. In contrast to numerous discoveries that reveal the detailed mechanisms leading to the formation of the primary tumor, the biological underpinnings of the metastatic disease remain poorly understood. Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle, and grow at other parts of the body. Epithelial‐mesenchymal transition and anoikis resistance of tumor cells are the main forces to promote metastasis, and multiple components in the tumor microenvironment and their complicated crosstalk with cancer cells are closely involved in distant metastasis. In addition to the three cornerstones of tumor treatment, surgery, chemotherapy, and radiotherapy, novel treatment approaches including targeted therapy and immunotherapy have been established in patients with metastatic cancer. Although the cancer survival rate has been greatly improved over the years, it is still far from satisfactory. In this review, we provided an overview of the metastasis process, summarized the cellular and molecular mechanisms involved in the dissemination and distant metastasis of cancer cells, and reviewed the important advances in interventions for cancer metastasis.

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“…The potential use of the produced nanoparticles as antimicrobial materials against cancer-related, opportunistic bacterial strains was finally tested for a battery of five standard strains: E. coli [ 76 ], S. aureus [ 77 ], MRSA [ 78 ], P. aeruginosa [ 79 ] and E. faecalis [ 80 ]. These standard strains were selected due to their identified relationship, and locality, to some types of tumors, as well as their known response to the selected drugs [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer

Marcelo¹,

Galhano²,

Robalo³

et al. 2022

IJMS

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Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin–ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.

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Pulmonary Staphylococcus aureus infection regulates breast cancer cell metastasis via neutrophil extracellular traps (NETs) formation

Cited by 17 publications

References 41 publications

Improved radiation expression profiling in blood by sequential application of sensitive and specific gene signatures

Improved radiation expression profiling in blood by sequential application of sensitive and specific gene signatures

Tumor metastasis: Mechanistic insights and therapeutic interventions

Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer

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