Exosomes derived from breast cancer lung metastasis subpopulations promote tumor self-seeding

Huang, Hongyun; Zheng, X.F. Steven; Cai, Changqing; Yao, Zhuocheng; Lu, Sitong; Meng, Xiang‐Jin; Miao, Yutian; He, Zhanxin; Cheng, Can; Zou, Fei

doi:10.1016/j.bbrc.2018.06.009

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…Tumor-derived exosomes (TDEs) have been shown to play a significant role in modifying the lung microenvironment. This is highlighted by recent studies involving pre-treatment of mouse models with TDEs from lung-seeking breast cancer cell lines that showed the potential to “educate” the lung, inducing changes that made it more susceptible to metastasis [50]. Exosomes secreted by the primary tumor have the ability to target the lung through use of integrins such as ITGα 6 β 1 [27].…”

Section: Tumor-derived Exosomesmentioning

confidence: 99%

Molecular Mechanisms of Breast Cancer Metastasis to the Lung: Clinical and Experimental Perspectives

Medeiros

Allan

2019

IJMS

183

118

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Breast cancer is the most commonly diagnosed cancer in women worldwide, and >90% of breast cancer-related deaths are associated with metastasis. Breast cancer spreads preferentially to the lung, brain, bone and liver; termed organ tropism. Current treatment methods for metastatic breast cancer have been ineffective, compounded by the lack of early prognostic/predictive methods to determine which organs are most susceptible to developing metastases. A better understanding of the mechanisms that drive breast cancer metastasis is crucial for identifying novel biomarkers and therapeutic targets. Lung metastasis is of particular concern as it is associated with significant patient morbidity and a mortality rate of 60–70%. This review highlights the current understanding of breast cancer metastasis to the lung, including discussion of potential new treatment approaches for development.

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Section: Tumor-derived Exosomesmentioning

confidence: 99%

Molecular Mechanisms of Breast Cancer Metastasis to the Lung: Clinical and Experimental Perspectives

Medeiros

Allan

2019

IJMS

183

118

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“…Exosomes from different sources in the tumor microenvironment play different regulatory roles in the growth and metastasis of tumors. Recently, a study revealed that exosomes derived from lung metastasis subpopulations of breast cancer cells promote tumor self-seeding 42. Interestingly, macrophages-derived exosomes have dualistic role in preventing and supporting tumor progression 43.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis

Yu¹,

Zhang²,

Zhang³

et al. 2019

J. Cancer

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Exosomes have recently become the subject of increasing research interest. Interactions between tumor and host cells via exosomes play crucial roles in the initiation, progression and invasiveness of breast cancer. In our study, we used exosomes isolated from a co-culture model of THP-1-derived macrophages exposed to apoptotic MCF-7 or MDA-MB-231 breast cancer cell line cells to investigate their effects on naïve MCF-7 or MDA-MB-231 cells in vitro and in vivo. This post-chemotherapy tumor microenvironment model allowed us to explore possible mechanisms that explain increased proliferation and metastasis of breast cancer seen in some patients. Our results suggest that while exosomes derived from macrophages normally inhibit proliferation and metastasis of MCF-7 or MDA-MB-231 cells, exposure of macrophages to breast cancer cells that have experienced chemotherapy are modified them to promote these processes. Exosomes from macrophages exposed to apoptotic cancer cells have increased amounts of IL-6 that increases the phosphorylation of STAT3, which likely explains the increased transcription of STAT3 target genes such as CyclinD1, MMP2 and MMP9. These observations suggest that the inhibition of exosome secretion and STAT3 signaling pathway activation might suppress the growth and metastasis of malignant tumors, and provide new targets for therapeutic treatment of malignant tumors after chemotherapy.

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“…A role for exosomes was proposed in tumor "self-seeding", a process by which cancer cells become able to reinfiltrate the original tumor. Indeed, it has been demonstrated that exosomes derived from a subpopulation of breast cancer lung metastasis, the MDA231-LM2, potentiate the growth of MDA-MB-231 in xenograft models [80]. In an elegant work, Hoshimo et al proved, in different mouse models, that the organ specificity of exosome biodistribution corresponds to the organotropic distribution of the cell line of origin.…”

Section: Metastatic Colonization and Growthmentioning

confidence: 99%

The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization

Giordano

Camera

Gelsomino

et al. 2020

Cancers

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In recent decades, the study of exosome biology has gained growing interest, representing an active area of cancer research with many potential clinical applications. Exosomes are small lipid bilayer particles released by cells with pleiotropic functions that have been reported to regulate the complex intracellular pathway involved in all steps of breast cancer development—from initiation to progression toward a metastatic dissemination. Particularly, the role of these microvesicles has been explored in metastasis, which represents the leading cause of breast cancer morbidity and mortality worldwide. Reports highlight that the plasticity of breast cancer cells, fundamental for the establishment of distant metastasis, may be in part attributed to exosome-carried signals shared between adjacent cells and long-distance cells in the body. In the present review, we will discuss the functions of exosomes in the metastatic breast cancer process and secondary site outgrowth. The possibility to decode the exosome functions in advanced diseases may offer new opportunities for early detection, molecular targeted therapies and exosome-based therapeutics in breast cancer.

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Exosomes derived from breast cancer lung metastasis subpopulations promote tumor self-seeding

Cited by 14 publications

References 23 publications

Molecular Mechanisms of Breast Cancer Metastasis to the Lung: Clinical and Experimental Perspectives

Molecular Mechanisms of Breast Cancer Metastasis to the Lung: Clinical and Experimental Perspectives

Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis

The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization

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