Liquid biopsies to occult brain metastasis

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Abstract

Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.

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Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Clotilde Théry, Kenneth W Witwer, Elena Aikawa … (2019)

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

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Inflammation and cancer.

Lisa Coussens, Zena Werb (2002)

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

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Tumour exosome integrins determine organotropic metastasis

Ayuko Hoshino, Bruno Costa-Silva, Tang-Long Shen … (2015)

Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

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Author and article information

Contributors

Mohd Wasim Nasser:

ORCID: http://orcid.org/0000-0003-2070-4972

wasim.nasser@unmc.edu

Journal

Journal ID (nlm-ta): Mol Cancer

Journal ID (iso-abbrev): Mol Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date (Electronic): 10 May 2022

Publication date PMC-release: 10 May 2022

Publication date Collection: 2022

Volume: 21

Electronic Location Identifier: 113

Affiliations

[1 ]GRID grid.266813.8, ISNI 0000 0001 0666 4105, Department of Biochemistry and Molecular Biology, , University of Nebraska Medical Center, ; Omaha, NE 68108 USA

[2 ]GRID grid.266813.8, ISNI 0000 0001 0666 4105, Fred and Pamela Buffett Cancer Center, , University of Nebraska Medical Center, ; Omaha, NE 68108 USA

[3 ]GRID grid.266813.8, ISNI 0000 0001 0666 4105, Department of Surgery, , University of Nebraska Medical Center, ; Omaha, NE 68108 USA

[4 ]GRID grid.266813.8, ISNI 0000 0001 0666 4105, Eppley Institute for Research in Cancer and Allied Diseases, , University of Nebraska Medical Center, ; Omaha, NE-68198 USA

Author information

Mohd Wasim Nasser http://orcid.org/0000-0003-2070-4972

Article

Publisher ID: 1577

DOI: 10.1186/s12943-022-01577-x

PMC ID: 9088117

PubMed ID: 35538484

SO-VID: 770e0255-9259-424a-9c81-97adadd1757c

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 15 December 2021

Date accepted : 19 April 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000054, National Cancer Institute;

Award ID: R01CA218545

Award ID: R01CA241752

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: P01 CA217798

Award Recipient : Surinder K. Batra

Funded by: FundRef http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;

Award ID: W81XWH-21-1-0640

Award Recipient : Jawed A. Siddiqui

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: ctcs,cell-free dna,microrna,brain microenvironment,cancer diagnostics,exosomes

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: ctcs, cell-free dna, microrna, brain microenvironment, cancer diagnostics, exosomes

Liquid biopsies to occult brain metastasis

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Abstract

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Karger: Oncology

Most cited references 201

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Inflammation and cancer.

Tumour exosome integrins determine organotropic metastasis

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