Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Aug 13;18(1):124.
doi: 10.1186/s12943-019-1049-4.

Exosomes promote pre-metastatic niche formation in ovarian cancer

Wenlong Feng  1   2 , Dylan C Dean  2 , Francis J Hornicek  2 , Huirong Shi  3 , Zhenfeng Duan  4   5
Affiliations
Review

Exosomes promote pre-metastatic niche formation in ovarian cancer

Wenlong Feng et al. Mol Cancer. .

Abstract

Ovarian cancer is one of the most common gynecological malignancies. Upon initial diagnosis, the majority of patients present with widespread metastatic growth within the peritoneal cavity. This metastatic growth occurs in stages, with the formation of a pre-metastatic niche occurring prior to macroscopic tumor cell invasion. Exosomes released by the primary ovarian tumor are small extracellular vesicles which prepare the distant tumor microenvironment for accelerated metastatic invasion. They regulate intercellular communication between tumor cells and normal stroma, cancer-associated fibroblasts, and local immune cells within the tumor microenvironment. In this review, we highlight the emerging roles of ovarian cancer exosomes as coordinators of pre-metastatic niche formation, biomarkers amenable to liquid biopsy, and targets of chemotherapy.

Keywords: Exosome; Metastasis; Ovarian cancer; Pre-metastatic niche.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
a. The biogenesis of exosomes and the mechanisms involved in intercellular communication. The exosome is an intraluminal vesicle (ILV) formed by the inward budding of the endosomal membrane during the maturation of the multivesicular endosomes (MVEs) and then secreted after fusing with the cell surface. Uptake by recipient cells occurs via a three step processes: 1. membrane fusion with target cells; 2. endocytosis; 3. activation of surface receptors and signaling. b. Schematic diagram of the exosome. The exosome is a disk-shaped membranous vesicle with a diameter 30–100 nm, and carries a parental cell cargo including lipids, metabolites, proteins, nucleic acids (DNA fragments, mRNA, miRNA, etc.)
Fig. 2
Fig. 2
Impact of ovarian cancer-exosomes on target cells during pre-metastatic niche formation. a. Ovarian cancer-exosomes induce apoptosis of dendritic cells, increase secretion of IL-6, and inhibit function of T cells and NK cells. b. Ovarian cancer-exosomes with their cargo, such as ATF2, MTA1, sE-cad, and CD147, which acts on human vein endothelial cells, inducing angiogenesis and vascular permeability. c. Ovarian cancer-exosomes convert fibroblasts to CAFs. d. Ovarian cancer-exosomes deliver miRNAs to macrophages and elicit M2 macrophage polarization by regulating the suppressor of cytokine signaling (SOCS)4/5/ STAT3 pathway in macrophages. e. Phenotypic conversion and apoptosis of PMCs, induced by ovarian cancer-exosomes, clears the mesothelial cell barrier of the peritoneum and omentum. OC ovarian cancer, NK natural killer, ATF2 Activating transcription factor 2, MTA1 Metastasis-associated protein 1, sE-cad soluble E-cadherin, SOCS Suppress cytokine signaling, STAT3 Signal transducer and activator of transcription 3, PMC Peritoneal mesothelial cell, CAF cancer-associated fibroblast
Fig. 3
Fig. 3
Two main methods of ovarian cancer metastasis within the peritoneal cavity, direct implantation and hematogenous spread. a Distribution of ovarian cancer nests in the peritoneal cavity. b Mechanisms of ovarian cancer-exosome establishment of the pre-metastatic niche before metastasis. c After the formation of pre-metastatic niche, tumor cells home to the metastatic site then colonize and support vessel budding. OC: ovarian cancer; NK: natural killer; HUVECs: Human umbilical vein endothelial cells; TAM: tumor-associated macrophages; PMC: Peritoneal mesothelial cell; CAF: cancer-associated fibroblasts.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Howlader N NA, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). Statistics Review, 1975-2014, National Cancer Institute. 2018.
    1. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A, Siegel RL. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68:284–296. doi: 10.3322/caac.21456. - DOI - PMC - PubMed
    1. Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014;384:1376–1388. doi: 10.1016/S0140-6736(13)62146-7. - DOI - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. doi: 10.3322/caac.21442. - DOI - PubMed
    1. Lee W, Ko SY, Mohamed MS, Kenny HA, Lengyel E, Naora H. Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum. J Exp Med. 2019;216:176–194. doi: 10.1084/jem.20181170. - DOI - PMC - PubMed

Publication types