Neuroblastoma (NB) is the second most common solid cancer in childhood, accounting for 15% of cancer-related deaths in children. In high-risk NB patients, the majority suffers from metastasis. Despite intensive multimodal treatment, long-term survival remains <40%. The bone marrow (BM) is among the most common sites of distant metastasis in patients with high-risk NB. In this environment, small populations of tumor cells can persist after treatment (minimal residual disease) and induce relapse. Therapy resistance of these residual tumor cells in BM remains a major obstacle for the cure of NB. A detailed understanding of the microenvironment and its role in tumor progression is of utmost importance for improving the treatment efficiency of NB. In BM, mesenchymal stromal cells (MSCs) constitute an important part of the microenvironment, where they support hematopoiesis and modulate immune responses. Their role in tumor progression is not completely understood, especially for NB. Although MSCs have been found to promote epithelial–mesenchymal transition, tumor growth, and metastasis and to induce chemoresistance, some reports point toward a tumor-suppressive effect of MSCs. In this review, we aim to compile current knowledge about the role of MSCs in NB development and progression. We evaluate arguments that depict tumor-supportive versus -suppressive properties of MSCs in the context of NB and give an overview of factors involved in MSC-NB crosstalk. A focus lies on the BM as a metastatic niche, since that is the predominant site for NB metastasis and relapse. Finally, we will present opportunities and challenges for therapeutic targeting of MSCs in the BM microenvironment.

中文翻译：

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神经母细胞瘤中的间充质基质细胞：探索串扰和治疗意义


神经母细胞瘤 (NB) 是儿童时期第二常见的实体癌症，占儿童癌症相关死亡的 15%。在高危NB患者中，大多数患有转移。尽管采用强化多模式治疗，长期生存率仍低于 40%。骨髓（BM）是高危 NB 患者最常见的远处转移部位之一。在这种环境中，少量肿瘤细胞在治疗后可以持续存在（微小残留病）并诱发复发。 BM 中这些残留肿瘤细胞的治疗耐药性仍然是 NB 治愈的主要障碍。详细了解微环境及其在肿瘤进展中的作用对于提高 NB 的治疗效率至关重要。在骨髓中，间充质基质细胞（MSC）构成微环境的重要组成部分，它们支持造血作用并调节免疫反应。它们在肿瘤进展中的作用尚不完全清楚，特别是对于 NB。尽管已发现间充质干细胞可促进上皮-间质转化、肿瘤生长和转移并诱导化疗耐药，但一些报告指出间充质干细胞具有肿瘤抑制作用。在这篇综述中，我们的目标是汇编有关 MSC 在 NB 发生和进展中的作用的最新知识。我们评估了在 NB 背景下描述 MSC 的肿瘤支持与抑制特性的论点，并概述了 MSC-NB 串扰所涉及的因素。重点在于 BM 作为转移生态位，因为这是 NB 转移和复发的主要部位。最后，我们将提出骨髓微环境中间充质干细胞治疗靶向的机遇和挑战。