肿瘤和淋巴结微环境之间的相互作用在头颈癌中形成淋巴结转移前生态位。
The interplay between tumor and nodal microenvironments for the formation of nodal pre-metastatic niche in head and neck cancer.
发表日期:2023 Nov 06
作者:
Nicholas S Mastronikolis, Despoina Spyropoulou, Efthymios Kyrodimos, Zoi Piperigkou, Evangelos Giotakis, Alexander Delides, Nikos K Karamanos
来源:
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
摘要:
头颈癌 (HNC) 包括多种起源于头颈部的恶性肿瘤。在 HNC 患者中,颈部淋巴结构成逃离原发肿瘤的癌细胞的转移部位。转移前生态位(PMN)是理解转移性疾病的关键概念。 PMN是指主要由原发性肿瘤细胞产生的、促进远处器官转移性肿瘤细胞生长的微环境。肿瘤微环境(TME)在PMN的发病机制中发挥着重要作用。一个重要的预后因素是许多不同恶性肿瘤中淋巴结转移与器官播散之间的密切相关性。淋巴结转移前生态位 (NPMN) 是位于淋巴结内的一种特殊类型的 PMN。 NPMN 的形成在 HNC 中特别重要,因为区域淋巴结转移经常发生。当肿瘤细胞在淋巴结内创造支持性微环境,促进其生存、生长、扩散和侵袭时,就会发生这种形成。这种复杂的机制涉及原发肿瘤和肿瘤微环境之间的多个步骤和细胞相互作用。几种细胞外基质(ECM)大分子、细胞因子和生长因子都参与了这个过程。本文的目的是介绍 HNC 中淋巴结 PMN 在分子和细胞水平上调控的最新数据,以及对原发肿瘤细胞与淋巴结微环境之间关系的见解,以及NPMN的形成。我们还批判性地讨论了预防或破坏淋巴结转移的潜在目标,并确定了预测 HNC 结果的潜在生物标志物。
Head and neck cancer (HNC) encompasses a number of malignancies originating in the head and neck area. In HNC patients, cervical lymph nodes constitute metastatic sites for cancer cells that escape primary tumors. The pre-metastatic niche (PMN) is a crucial concept in understanding metastatic disease. PMN refers to the microenvironment resulting mainly from primary tumor cells to foster metastatic tumor cells growth at a distant organ. Tumor microenvironment (TME) plays an important part in the pathogenesis of PMN. A significant prognostic factor is the close association between metastases of lymph node and organ dissemination in many different malignancies. The nodal pre-metastatic niche (NPMN) is a particular type of PMN located within the lymph nodes. NPMN formation is specifically important in HNC since regional lymph node metastasis commonly occurs. The formation happens when tumor cells create a supportive microenvironment within lymph nodes, facilitating their survival, growth, spread, and invasion. This complex mechanism involves multiple steps and cellular interactions between the primary tumor and tumor microenvironment. Several extracellular matrix (ECM) macromolecules, cytokines and growth factors are implicated in this process. The aim of this article is to present the most recent data on the regulation of the lymph node PMN at molecular and cellular level in HNC, as well as insights in respect to the relationship between primary tumor cells and the microenvironment of lymph nodes, and the formation of NPMN. We also critically discuss on potential targets for preventing or disrupting nodal metastases and identify potential biomarkers for predicting HNC outcomes.