Lung adenocarcinoma cell-derived exosomal miR-21 facilitates osteoclastogenesis

Xu, Zhen; Liu, Xingwang; Wang, Huisheng; Li, Jutao; Dai, Lei; Li, Jun; Dong, Congcong

doi:10.1016/j.gene.2018.05.008

Cited by 78 publications

(64 citation statements)

References 41 publications

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“…In conclusion, our results may provide support for the concept of an exosomal miR-21 influx originating from the tumour towards the stroma where it may trigger certain down-stream pathways to promote tumour growth, angiogenesis and metastasis 63–66. Investigation of tumour and SC communication via exosome networks may benefit from additional in situ immunohistochemical studies such as ours and provide a platform for a better understanding of the molecular mechanisms and targets of miR-21 in NSCLC.…”

Section: Discussionsupporting

confidence: 59%

MiR-21, EGFR and PTEN in non-small cell lung cancer: an in situ hybridisation and immunohistochemistry study

Marin¹,

Ofek²,

Bar³

et al. 2020

J Clin Pathol

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AimsTo analyse microRNA (miR)-21 distribution and expression at the cellular level in non-small cell lung cancer (NSCLC). MiR-21 is an oncogenic microRNA overexpressed in NSCLC. In previous studies, overexpression of miR-21 was evaluated from the tumour bulk by quantitative reverse transcription PCR with results expressed on average across the entire cell population.MethodsWe used in situ hybridisation and immunohistochemistry to assess the correlation between miR-21 levels and the expression of markers that may be possible targets (epidermal growth factor reaction) or may be involved in its upregulation (phosphatase and tensin homolog (PTEN), p53). The Pearson’s χ2 tests was used to assess correlation with clinicopathological data and with miR-21 expression both in tumour and tumour stroma.ResultsCytoplasmic staining and expression of Mir-21 were detected in the tumours and in associated stromal cells. Expression was highest in the stroma immediately surrounding the tumour cells and decreased as the distance from the tumour increased. No expression of miR-21 was found in normal lung parenchyma and a significant association was found between tumour localised miR-21 and PTEN.ConclusionsPresence of miR-21 in both cell tumour and stromal compartments of NSCLC and the relationship with PTEN confirms miR-21 as a microenvironment signalling molecule, possibly inducing epithelial mesenchymal transition and invasion by targeting PTEN in the stromal compartment possibly through exosomal transport. In situ immunohistochemical studies such as ours may help shed light on the complex interactions between miRNAs and its role in NSCLC biology.

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Section: Discussionsupporting

confidence: 59%

MiR-21, EGFR and PTEN in non-small cell lung cancer: an in situ hybridisation and immunohistochemistry study

Marin¹,

Ofek²,

Bar³

et al. 2020

J Clin Pathol

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“…AREG knockdown, neutralization with AREG antibodies, and cotreatment with NSCLC-EVs and the epidermal growth factor receptor–tyrosine kinase inhibitor erlotinib reversed EV-induced osteoclast differentiation. Moreover, Xu et al found that treatment of bone marrow-derived monocytes with adenocarcinoma-derived EVs promoted osteoclast formation by shuttling miR-21, which in turn inhibited Pdcd4, a transcription factor involved in osteoclastogenesis [ 75 ].…”

Section: Bone Metastasis and Evsmentioning

confidence: 99%

Extracellular Vesicles in Bone Metastasis: Key Players in the Tumor Microenvironment and Promising Therapeutic Targets

Tamura

Yoshioka

Sakamoto

et al. 2020

IJMS

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Extracellular vesicles (EVs) are lipid membranous vesicles that are released from every type of cell. It has become clear that EVs are involved in a variety of biological phenomena, including cancer progression, and play critical roles in intracellular communication through the horizontal transfer of cellular cargoes such as proteins, DNA fragments, RNAs including mRNA and non-coding RNAs (microRNA, piRNA, and long non-coding RNA) and lipids. The most common cause of death associated with cancer is metastasis. Recent investigations have revealed that EVs are deeply associated with metastasis. Bone is a preferred site of metastasis, and bone metastasis is generally incurable and dramatically affects patient quality of life. Bone metastasis can cause devastating complications, including hypercalcemia, pathological fractures, spinal compression, and bone pain, which result in a poor prognosis. Although the mechanisms underlying bone metastasis have yet to be fully elucidated, increasing evidence suggests that EVs in the bone microenvironment significantly contribute to cancer progression and cancer bone tropism. Emerging evidence on EV functions in bone metastasis will facilitate the discovery of novel treatments. In this review, we will discuss the remarkable effects of EVs, especially on the tumor microenvironment in bone.

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“…In addition to single exosomal protein factors, multiple miRNAs have also been identified in promoting tumor metastasis. Xu et al reported that lung adenocarcinoma cell derived exosomal miR-21 facilitated osteoclastogenesis, which is correlated to tumor osteolytic metastasis [73]. Another study by Yang et al demonstrated that exosomal miR-423-5p promote cancer cell growth and metastasis by repression of SUFU protein expression, which enhance the proliferation and migration in recipient gastric cells [74].…”

Section: Exosomes In Tumor Microenvironment and Their Role In Immumentioning

confidence: 99%

Exosomes, Their Biogenesis and Role in Inter-Cellular Communication, Tumor Microenvironment and Cancer Immunotherapy

et al. 2018

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Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain molecular constituents of their host cells. They are released from different types of cells ranging from immune to tumor cells and play an important role in intercellular communication. Exosomes can be manipulated by altering their host cells and can be loaded with products of interest such as specific drugs, proteins, DNA and RNA species. Due to their small size and the unique composition of their lipid bilayer, exosomes are capable of reaching different cell types where they alter the pathophysiological conditions of the recipient cells. There is growing evidence that exosomes are used as vehicles that can modulate the immune system and play an important role in cancer progression. The cross communication between the tumors and the cells of the immune system has gained attention in various immunotherapeutic approaches for several cancer types. In this review, we discuss the exosome biogenesis, their role in inter-cellular communication, and their capacity to modulate the immune system as a part of future cancer immunotherapeutic approaches and their potential to serve as biomarkers of therapy response.

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Lung adenocarcinoma cell-derived exosomal miR-21 facilitates osteoclastogenesis

Cited by 78 publications

References 41 publications

MiR-21, EGFR and PTEN in non-small cell lung cancer: an in situ hybridisation and immunohistochemistry study

MiR-21, EGFR and PTEN in non-small cell lung cancer: an in situ hybridisation and immunohistochemistry study

Extracellular Vesicles in Bone Metastasis: Key Players in the Tumor Microenvironment and Promising Therapeutic Targets

Exosomes, Their Biogenesis and Role in Inter-Cellular Communication, Tumor Microenvironment and Cancer Immunotherapy

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