Pre-metastatic niche: from revealing the molecular and cellular mechanisms to the clinical applications in breast cancer metastasis

Sep 24, 2026

Uploaded by Theodore

Breast cancer is a leading cause of cancer mortality in women, largely driven by metastasis. Metastasis follows sequential, dynamic events culminating in invasion and colonization, preceded by formation of a pre-metastatic niche (PMN). PMN creates a supportive environment that enables tumor cells to progress into metastases. The review synthesizes how altered molecules, immune-cell functions, stromal remodeling, angiogenesis, metabolic reprogramming, and organotropism coordinate PMN development, emphasizing diagnostic and therapeutic opportunities.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Introduction

Metastasis and the “seed and soil” framework

Mechanisms triggering PMN formation

The formation of PMN

Review Ivyspring International Publisher Theranostics 2023; 13(7): 2301-2318. doi: 10.7150/thno.82700 Pre-metastatic niche: from revealing the molecular and cellular mechanisms to the clinical applications in breast cancer metastasis Yuqiu Li1,2†, Miao Li1,3†, Kangtai Su4, Siwen Zong3, Hongyan Zhang5􀀍, Lixia Xiong1􀀍 1. Department of Pathophysiology, Medical College, Nanchang University, 461 Bayi Road, Nanchang 330006, China. 2. Queen Mary College of Nanchang University, Nanchang 330006, China. 3. Second Clinical Medical College, Nanchang University, Nanchang 330006, China. 4. First Clinical Medical College, Nanchang University, Nanchang 330006, China. 5. Department of Burn, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Road, Nanschang 330066, China. †These authors have contributed equally to this work and share the first authorship. 􀀍 Corresponding authors: Hongyan Zhang and Lixia Xiong; email: [ndyfy00672@ncu.edu.cn and](ndyfy00672@ncu.edu.cn and) [xionglixia@ncu.edu.cn](xionglixia@ncu.edu.cn) © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [http://ivyspring.com/terms](http://ivyspring.com/terms) for full terms and conditions. Received: 2023.01.16; Accepted: 2023.04.08; Published: 2023.04.17 Abstract Breast cancer (BC) is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths in women worldwide. Metastasis is a major contributor to high cancer mortality and is usually the endpoint of a series of sequential and dynamic events. One of the critical events is forming a pre-metastatic niche (PMN) that occurs before macroscopic tumor cell invasion and provides a suitable environment for tumor cells to colonize and progress into metastases. Due to the unique characteristics of PMN in cancer metastasis, developing therapies to target PMN may bring new advantages in preventing cancer metastasis at an early stage. Various biological molecules, cells, and signaling pathways are altered in BC, regulating the functions of distinctive immune cells and stromal remodeling, inducing angiogenesis, and effect metabolic reprogramming and organotropism to promote PMN formation. In this review, we elucidate the multifaceted mechanisms contributing to the development of PMN in BC, discuss the characteristics of PMN, and highlight the significance of PMN in providing potential diagnostic and therapeutic strategies for BC metastasis, which may bring promising insights and foundations for future studies. Introduction According to cancer data in 2023, breast cancer (BC) has overtaken lung cancer as the most common cancer in women worldwide [1] . It is also the leading cause of cancer-related death, with metastases to vital organs remaining the leading cause of death in BC patients [2] . Several studies have revealed that BC metastasis is heterogeneous, with different metastatic priorities in different organs. Bone, lung, liver, and brain are commonly considered to be the main targets of BC metastases [3] . This organotropism leads to differentiation in prognosis and the effects of treatment in patients with BC. Therefore, it is important to identify pivotal molecular and cellular components in any cancer metastasis process and develop novel strategies for the early detection and treatment of BC patients. The process of metastasis is complicated, and multiple molecules and events contribute to this process. One of the vital steps in cancer metastasis is the formation of a metastatic microenvironment [3] . Proposed in 1889, Stephen Paget illustrated that metastasis depends on the interactions between "seed"(or cancer cells) and "soil" (or host microenvironment), opening new directions for understanding the metastatic process and the phenomenon of organotropism. Further research suggested

FAQs

What is a pre-metastatic niche (PMN) in breast cancer metastasis?

A PMN is a cancer-cell-free microenvironment formed before macroscopic tumor invasion. It provides conditions that help tumor cells colonize and progress in distant organs.

Which mechanisms contribute to PMN formation in breast cancer?

PMN formation involves changes in biological molecules, immune regulation, stromal remodeling, angiogenesis/vascular permeability, organotropism, and metabolic reprogramming.

How does targeting PMN may help prevent breast cancer metastasis?

Because PMN develops early and supports later metastatic establishment, therapies aimed at PMN-promoting processes may provide advantages for preventing metastasis at an earlier stage.

Sep 24, 2026

Uploaded by Theodore