Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation

Sep 24, 2026

Uploaded by Rowan

Metastasis is a multi-step cancer process responsible for most cancer-related deaths. Metabolic reprogramming describes adaptive metabolic rewiring in tumor cells within the tumor microenvironment (TME) that increases survival and metastatic ability. Stromal cells also undergo metabolic shifts to support tumor growth. Such adaptations extend beyond the TME into the pre-metastatic niche (PMN). Small extracellular vesicles (sEVs) act as mediators of sEV-driven metabolic reprogramming and can deliver proteins, mRNAs and miRNAs from tumors to PMN, promoting niche formation, angiogenesis, immune suppression and matrix remodeling, with implications for diagnosis and therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

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Abstract

Background

Tumor metastasis and pre-metastatic niche (PMN)

Tumor microenvironment components and cell communication

Metabolic reprogramming as a hallmark of cancer

Role of sEVs in metabolic regulation and metastatic spread

sEV cargoes and therapeutic potential

Jiang et al. Cell Communication and Signaling (2023) 21:116 [https://doi.org/10.1186/s12964-023-01136-x](https://doi.org/10.1186/s12964-023-01136-x) Cell Communication and Signaling REVIEW Open Access Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation Chuwen Jiang1†, Zhengting Jiang1†, Gengyu Sha1†, DaorongWang2 and Dong Tang2* Abstract Metastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in theTME but also in the pre-metastatic niche (PMN), a remoteTME conducive for tumor metastasis. As a novel mediator in cellto-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30–150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs) . sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment. Keywords sEVs, Metabolic reprogramming, Tumor microenvironment, PMN, Metastasis Background Tumor metastasis is a process whereby tumor cells migrate from a primary site to distant organs and tissues progressively, resulting in the majority deaths among tumor patients [1]. The establishment of the pre-metastasis niche (PMN), a favorable tumor microenvironment (TME) in a distant metastatic organ, is a prerequisite to †Chuwen Jiang, Zhengting Jiang and Gengyu Sha have contributed equally to this work and share first authorship. *Correspondence: Dong Tang [83392785@qq.com](83392785@qq.com) 1 Clinical Medical College, Yangzhou University, Yangzhou 225001, Jiangsu Province, China 2 Department of General Surgery, Institute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People’s Hospital, Yangzhou 225001, China sustain the remote settlement of tumor cells and accelerate metastasis [2]. TME is a highly complicated and heterogeneous ecosystem that is composed of tumor cells, fibroblasts, adipocyte cells, endothelial cells (ECs), mesenchymal stem cells (MSCs), and extracellular matrix [3]. Extensive communication between cancer cells and otherstromal cells including autocrine and paracrine signal transduction in TME could regulate apoptosis inhibition, immunosuppression, angiogenesis, and metabolic reprogramming, thereby affecting tumor malignant progression like metastasis [3, 4]. Metabolic reprogramming refers to the process wherein the glucose, lipid and amino acid metabolism of cancer cells change adaptively to help them quickly proliferate and survive under the high pressure of environment whether in the primary TME or PMN [5]. As tumor cells reprogram metabolism in every step of tumor © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included

FAQs

What does metabolic reprogramming mean in cancer progression?

Metabolic reprogramming refers to adaptive changes in glucose, lipid, and amino acid metabolism that help cancer cells proliferate and survive under environmental pressure, both in the primary TME and in the PMN.

How are pre-metastatic niches (PMN) formed and why are they important?

PMN are favorable distant tumor microenvironments that enable remote settlement of tumor cells and accelerate metastasis. They are established as a prerequisite for metastatic growth.

How do small extracellular vesicles (sEVs) contribute to metastasis?

sEVs (30–150 nm) transfer bioactive cargo such as proteins, mRNAs, and miRNAs between tumor and stromal cells. They can move from the primary TME to the PMN and promote niche formation by influencing processes like angiogenesis, immunological suppression, and matrix cell metabolism.

Sep 24, 2026

Uploaded by Rowan