Restoring Tissue Homeostasis at Metastatic Sites: A Focus on Extracellular Vesicles in Bone Metastasis

Giannandrea, Domenica; Citro, Valentina; Lesma, Elena; Bignotto, Monica; Platonova, N.; Chiaramonte, R.

doi:10.3389/fonc.2021.644109

Cited by 14 publications

(10 citation statements)

References 121 publications

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“…Moreover, we are the first to provide evidence that miR-92a-3p is enriched in 4T1-EVs and that it plays an important role in regulating mature osteoclast survival by targeting PTEN (Figure 7). Despite accumulating evidence linking mammary tumor cellderived EVs to bone metastatic process, 25 the precise mechanisms through which cancer cell-derived EVs regulate bone microenvironments are still under investigation. In our in vitro studies, BMM and RAW264.7 cell treatment with 4T1-EVs markedly facilitated RANKL-induced osteoclastogenesis, compared with 67NR-EV treatment.…”

Section: Discussionmentioning

confidence: 99%

miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

et al. 2022

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Aberrant osteoclast formation and activation are the hallmarks of osteolytic metastasis. Extracellular vesicles (EVs), released from bone metastatic tumor cells, play a pivotal role in the progression of osteolytic lesions. However, the mechanisms through which tumor cell–derived EVs regulate osteoclast differentiation and function have not been fully elucidated. In this study, we found that 4T1 bone metastatic mouse mammary tumor cell–derived EVs (4T1‐EVs) are taken up by mouse bone marrow macrophages to facilitate osteoclastogenesis. Furthermore, treatment of mature osteoclasts with 4T1‐EVs promoted bone resorption, which was accompanied by enhanced survival of mature osteoclasts through the negative regulation of caspase‐3. By comparing the miRNA content in 4T1‐EVs with that in 67NR nonmetastatic mouse mammary tumor cell–derived EVs (67NR‐EVs), miR‐92a‐3p was identified as one of the most enriched miRNAs in 4T1‐EVs, and its transfer into mature osteoclasts significantly reduced apoptosis. Bioinformatic and Western blot analyses revealed that miR‐92a‐3p directly targeted phosphatase and tensin homolog (PTEN) in mature osteoclasts, resulting in increased levels of phospho‐Akt. Our findings provide novel insights into the EV‐mediated regulation of osteoclast survival through the transfer of miR‐92a‐3p, which enhances mature osteoclast survival via the Akt survival signaling pathway, thus promoting bone resorption.

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Section: Discussionmentioning

confidence: 99%

miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

et al. 2022

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“…При опухолях височных костей запускаются иммунные ответы организма, где ключевую роль играет повышение концентрации провоспалительных веществ (цитокины, интерлейкины, простагландины), выделяемых активированными макрофагами, моноцитами и лейкоцитами. Это приводит к ремоделированию костной ткани на пути роста опухоли и в конечном итоге -к образованию дефектов височной кости [8][9][10][11][12][13].…”

Section: Discussionunclassified

: 6

Дайхес¹,

Diab²,

Pashchinina³

et al. 2021

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Введение. Височная кость представляет собой трудную хирургическую область, так как здесь расположены органы слуха, равновесия, достаточно сложный по своему строению лицевой нерв, крупные сосуды (внутренняя сонная артерия, луковица яремной вены) и синусы височной кости. Все это, а также близость мозга являются значительным препятствием для хирургии основания черепа. Цель. Описать клинические случаи выявленных редких злокачественных опухолей височной кости у пациентов, которые были оперированы в отделе патологии уха и основания черепа. Материалы и методы. С октября 2014 до мая 2021 года проведено обследование и хирургическое лечение 175 пациентов с различными опухолями латерального основания черепа. Среди этих 175 (100%) пациентов на долю редких новообразований (различной морфологии) пришелся 21 (12,0%) случай наблюдений. При этом из 21 пациента с редкими новообразованиями на долю злокачественных редких опухолей пришлось 28,6% случаев, в отличие от доброкачественных, которые составляли большинство наблюдений - 71,4% случаев. Злокачественные опухоли составили 6 из 175 (частота встречаемости 10,5%) случаев. Анализ и описание серии случаев. Среди выявленных злокачественных опухолей рабдомиосаркома была диагностирована в половине случаев, преимущественно у пациентов детского возраста с частотой встречаемости 1,7%. Злокачественная низкодифференцированная опухоль солидного строения, опухоль эндолимфатического мешка и нейроэндокринная карцинома встречались с частотой 0,6% случаев каждая. Обсуждение. КТ и МРТ - это два взаимодополняющих метода исследования, позволяющих провести предварительную дифференциальную диагностику и определить предполагаемый объем операции в пользу возможного максимального сохранения анатомических структур височной кости. Выбор тактики лечения основывается на возрасте пациента, а также на соотношении пользы проводимой операции и риска рецидива. В некоторых случаях оправдан риск пожертвовать остатком слуха, чтобы опухоль могла быть полностью удалена. Если слуховая функция не сохранена исходно, то в данной ситуации возможным считается использование транслабиринтного подхода. Что касается лицевого нерва, то отохирург должен владеть хорошими навыками, чтобы, не повреждая ствол лицевого нерва, при необходимости смещать его для полноценной санации опухолевого процесса. Заключение. Отохирургу необходимо хорошо знать гистологическую гамму опухолей височных костей, следить за современным состоянием развития патологической анатомии черепа по литературным данным. Разработанные безопасные операционные доступы к различным областям височной кости, современные возможности ангиографии с селективной эмболизацией сосудов сделали возможным проводить резекцию даже запущенных опухолей. Использование вспомогательного оборудования (современные навигационные системы, нейромониторинг лицевого нерва и эндоскопическая ассистенция) позволило проводить такие операции с минимальным риском повреждения жизненно важных структур. Introduction. Difficulties of treatment of patients with tumors of the temporal bone are that the temporal bone represents difficult surgical area as the organ of hearing, balance, facial nerve, large vessels (internal carotid, bulb of the jugular vein), and sinuses of the temporal bone are located here. All this and also the proximity of the brain are a considerable obstacle for skull base surgery. Purpose. To describe clinical cases of the detected rare malignant tumors of the temporal bone in patients who were operated at the department of pathology of the ear and skull base. Materials and methods. From October 2014 to May 2021, the survey and surgical treatment of 175 patients with various tumors of the lateral skull base was carried out. Among these 175 (100%) patients, the share of rare neoplasms (various morphology) was 21 (12.0%). At the same time, from 21 patients with rare neoplasms, 28.6% of cases were the ones of rare malignant neoplasms, unlike benign tumors that made the majority of observations - 71.4%. Malignant tumors made 6 of 175 (the frequency of occurrence - 10.5%) cases. Analysis and description of a series of cases. Among the detected malignant tumors, rhabdomyosarcoma was revealed in half of cases, mainly in children with the frequency of occurrence of 1.7%. The malignant low-differentiated solid tumor, the tumor of endolymphatic bag, and neuroendocrine carcinoma were revealed with the frequency of 0.6% each. Discussion. CT and MRI are two complementary research methods that allowi to carry out preliminary differential diagnostics and to determine the preliminary volume of operation for possible maximum preservation of anatomical structures of the temporal bone. The choice of tactics of treatment is based on age of the patient and ratio of advantage of the performed operation and risk of recurrence. The risk is in certain cases justified to sacrifice the rest of hearing so that the tumor could be completely removed. If acoustical function is not kept initially, then the use of translabyrinth approach in this situation is possible. As for facial nerve, the otosurgeon must be highly skilled so that to displace the facial nerve without damaging it for full sanitation of the tumor process. Conclusion. There is still the need to study the histologic scale of tumors of temporal bones met in literature. The developed safe operational accesses to various areas of the temporal bone, modern opportunities of angiography with selection embolization of vessels let to carry out a resection even in advanced tumors. Use of the service equipment, such as modern navigation systems, neuromonitoring of the facial nerve, and endoscopic assistance let to perform such operations with minimal risk of damage to the vital structures.

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“…Extracellular vesicles are important mediators of cell-cell communication by carrying multiple active biomolecules including RNA, DNA, and proteins [288]. Growing evidence supports diverse roles for tumor-derived exosomes in conditioning bone stromal cells to prepare a "premetastatic niche" [289]. Exosomes derived from PC cell lines with different osteolytic abilities and from patients with PC, increased BM burden in a murine model and induced bone stromal cells to secrete the chemokine CXCL12 [290].…”

Section: Other Bone Invasive Pathwaysmentioning

confidence: 99%

Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment

Sethakorn

Héninger

Sánchez-de-Diego

et al. 2022

Cancers

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Bone metastases represent a lethal condition that frequently occurs in solid tumors such as prostate, breast, lung, and renal cell carcinomas, and increase the risk of skeletal-related events (SREs) including pain, pathologic fractures, and spinal cord compression. This unique metastatic niche consists of a multicellular complex that cancer cells co-opt to engender bone remodeling, immune suppression, and stromal-mediated therapeutic resistance. This review comprehensively discusses clinical challenges of bone metastases, novel preclinical models of the bone and bone marrow microenviroment, and crucial signaling pathways active in bone homeostasis and metastatic niche. These studies establish the context to summarize the current state of investigational agents targeting BM, and approaches to improve BM-targeting therapies. Finally, we discuss opportunities to advance research in bone and bone marrow microenvironments by increasing complexity of humanized preclinical models and fostering interdisciplinary collaborations to translational research in this challenging metastatic niche.

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Restoring Tissue Homeostasis at Metastatic Sites: A Focus on Extracellular Vesicles in Bone Metastasis

Cited by 14 publications

References 121 publications

miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

miR‐92a‐3p encapsulated in bone metastatic mammary tumor cell–derived extracellular vesicles modulates mature osteoclast longevity

: 6

Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment

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