Do tumor exosome integrins alone determine organotropic metastasis?
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REVIEW
Do tumor exosome integrins alone determine organotropic metastasis? E. S. Grigoryeva1 · O. E. Savelieva2 · N. O. Popova3 · N. V. Cherdyntseva1 · V. M. Perelmuter2 Received: 9 March 2020 / Accepted: 7 September 2020 © Springer Nature B.V. 2020
Abstract Metastasis is the most life-threatening event in cancer patients, so the key strategy to treat cancer should be preventing tumor spread. Predicting the site of probable hematogenous metastasis is important for determining the therapeutic algorithm that could prevent the spread of tumor cells. Certain hopes for solving this problem appeared owing to study showing the association between specific integrins on tumor exosomes surface and the site of future metastasis. Numerous experimental data indicate the ability of exosomes to transfer various phlogogenic factors to the target organ, which can lead to the formation of inflammatory foci. Studies of T-lymphocytes homing show that expression of various adhesion molecules including ligands for integrins highly increases on the endothelium during inflammation. Such a mechanism underlies not only in leukocyte transvasation, but, apparently, in the accumulation of bone marrow precursor cells and the formation of a premetastatic niche. This review summarizes the most significant data on the role exosomes to induce inflammation, which leads to the recruiting of bone marrow precursors and the establishment of premetastatic niches. Keywords Exosomes · Integrins · Organotropic metastasis · Carcinoma · Premetastatic niche
Introduction Despite significant advances in the diagnosis and treatment of cancer the occurrence of distant metastases is still the main cause of death in cancer patients. Prevention of tumor metastasis is the main goal of malignant tumors treatment. For a long time it was supposed that metastasis is a stochastic process and the direction of metastasis is determined by the anatomical features of the blood and lymphatic outflow from the primary tumor. Indeed, anatomical features fully explain the spread of tumor cells to regional lymph nodes or
* E. S. Grigoryeva [email protected] 1
Department of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk 634050, Russian Federation
2
Department of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Savinyh Str. 12/1, Tomsk 634028, Russian Federation
3
Department of Chemotherapy, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk 634050, Russian Federation
hematogenous metastasis of colon cancer in liver. However, the occurrence of bone marrow metastases in kidney, breast or lung cancer cannot be explained solely by the features of the anatomical structure. In accordance with modern concepts, metastasis is the result of two simultaneously developing processes: the appearance of cancer cell clone with the properties of “seeds”; and the occurrence of favorable conditions in t
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