Solid tumors’ metastasis mechanisms into the brain

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Abstract

The engineering and introduction into clinical practice of innovative methods of therapy patients with malignant tumors over the past two decades has certainly led to a significant increase in survival, which does not imply a “cure”, but the fact that more and more patients will live to the stage of metastasis to the central nervous system. The data obtained during diagnostic magnetic resonance imaging in recent years indicates a tendency to increase the number of cases of secondary brain damage in patients with various oncopathologies. Metastasis in the central nervous system is an actual problem due to the fact that the annual survival rate remains very low even with specific antitumor therapy (20 %). The study of the mechanisms of metastasis in the central nervous system is a key factor in the development of new effective approaches to the treatment of patients with this pathology, and, as a result, will lead to an improvement in the prognosis in this group of patients. Due to the analysis of the scientific literature on this issue, we have formulated and presented a modern understanding of the processes occurring in secondary brain damage. Special attention is devoted to organotropism, the mechanism of escape of metastatic cells from the immune system of the central nervous system and interaction with nerve cells, as well as the features of the extracellular matrix of the metastasis. Promising treatment methods being developed are presented.

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About the authors

Sofia S. Sklyar

Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre

Author for correspondence.
Email: s.sklyar2017@yandex.ru
ORCID iD: 0000-0002-3284-9688
SPIN-code: 4679-3548

MD, PhD, Senior Researcher of Research Laboratory of Neurooncology

Russian Federation, Saint Petersburg

Bobir I. Safarov

Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre

Email: safarovbob@mail.ru
ORCID iD: 0000-0002-2369-7424

MD, PhD, Head of 4th Department Neurooncology

Russian Federation, Saint Petersburg

Alexandr P. Trashkov

National Research Center “Kurchatov Institute”

Email: alexandr.trashkov@gmail.com
ORCID iD: 0000-0002-3441-0388
SPIN-code: 4231-1258

MD, PhD, Head of the Neurocognitive Research Resource Center

Russian Federation, Moscow

Ekaterina Yu. Zorina

Almazov National Medical Research Centre

Email: bryk74@mail.ru
ORCID iD: 0000-0002-5928-9625
SPIN-code: 3132-7676

MD, PhD, oncologist of Department of Surgical Methods of Treatment of Patients with a Cancer

Russian Federation, Saint Petersburg

Aleksandra M. Konova

Almazov National Medical Research Centre

Email: alex79696@mail.ru
ORCID iD: 0009-0004-7104-8447

oncologist of Department of Surgical Methods of Treatment of Patients with a Cancer

Russian Federation, Saint Petersburg

Victoria S. Kushnirova

Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre

Email: victoria.kushnirova@mail.ru
ORCID iD: 0000-0003-0480-0884
SPIN-code: 9105-5852

neurosurgeon

Russian Federation, Saint Petersburg

Konstantin K. Kukanov

Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre

Email: kukanov_kk@almazovcentre.ru
ORCID iD: 0000-0002-1123-8271
SPIN-code: 8938-0675

MD, PhD, Senior Researcher of Research Laboratory of Neurooncology

Russian Federation, Saint Petersburg

Anastasiia S. Nechaeva

Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre

Email: nastja-nechaeva00@mail.ru
ORCID iD: 0000-0001-9898-5925
SPIN-code: 2935-0745

Junior Researcher of Research Laboratory of Neurooncology

Russian Federation, Saint Petersburg

Viktor E. Olyushin

Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre

Email: fed_56@mail.ru
ORCID iD: 0000-0002-9960-081X

MD, PhD, Dr. Sci. (Medicine), Professor, Chief Scientific officer Research Laboratory of Neurooncology

Russian Federation, Saint Petersburg

Konstantin A. Samochernykh

Polenov Russian Neurosurgical Institute — the branch of Almazov National Medical Research Centre

Email: samochernykh_ka@almazovcentre.ru
ORCID iD: 0000-0003-0350-0249
SPIN-code: 4188-9657
Scopus Author ID: 24280115200
ResearcherId: AAS-7689-2020

Dr. Sci. (Medicine), professor, Director

Russian Federation, Saint Petersburg

Andrei G. Vasiliev

Saint Petersburg State Pediatric Medical University

Email: avas7@mail.ru
ORCID iD: 0000-0002-8539-7128
SPIN-code: 1985-4025

MD, PhD, Dr. Sci. (Medicine), Professor, Head of Pathophysiology Department

Russian Federation, Saint Petersburg

Anna V. Vasilieva

Saint Petersburg State Pediatric Medical University

Email: a-bondarenko@yandex.ru
ORCID iD: 0009-0008-2356-1552
SPIN-code: 5333-0144

Assistant of the Department of Pathological Physiology with the Course of Immunopathology

Russian Federation, Saint Petersburg

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2. Figure. Mechanism of metastasis into brain. A — Tumor cells from the primary tumor site are selected in accordance with phenotype suitable for metastasis into brain and get into blood-flow. Tumor cells are capable of emitting vesicles and exosomes with various micro-RNA and enzymes into blood-flow; B — with blood-flow metastatic tumor cells find their way into the brain; C — exosomes and vesicles expressed by the tumor cells affect and destroy cascade hematoencephalic barrier; D — having permeated into brain parenchyma, metastatic tumor cells may either transform into sleeping state or undergo adaptation stage right away (by means of new mutations) and form a secondary tumor site; Е — tumor cells constitute slit-like contacts with astrocytes for transition of metabolites and produce cytokines attracting myeloid cells that also differentiate under the influence of the tumor-associated macrophages

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