Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Adv Exp Med Biol. 2020;1226:37-50. doi: 10.1007/978-3-030-36214-0_3.
Parathyroid tumors are the second most common endocrine neoplasia, and it is almost always associated with hypersecretion of the parathormone (PTH), involved in calcium homeostasis, causing primary hyperparathyroidism (PHPT). Parathyroid neoplasia has a stromal component particularly represented in atypical adenomatous and carcinomatous lesions. Recently, data about the features and the function of the parathyroid tumor microenvironment (TME) have been accumulated. Parathyroid TME includes heterogeneous cells: endothelial cells, myofibroblasts, lymphocytes and macrophages, and mesenchymal stem cells have been identified, each of them presenting a phenotype consistent with tumor-associated cells. Parathyroid tumors overexpress proangiogenic molecules including vascular endothelial growth factor (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietins that promote both recruitment and proliferation of endothelial cell precursors, thus resulting in a microvessel density higher than that detected in normal parathyroid glands. Moreover, parathyroid tumor endocrine cells operate multifaceted interactions with stromal cells, partly mediated by the CXCL12/CXCR4 pathway, while, at present, the immune landscape of parathyroid tumors has just begun to be investigated. Studies about TME in parathyroid adenomas provide an example of the role of TME in benign tumors, whose molecular mechanisms and functions comprehension are limited.
甲状旁腺肿瘤是第二大常见的内分泌肿瘤，几乎总是与甲状旁腺激素 (PTH) 的过度分泌有关，PTH 参与钙稳态，导致原发性甲状旁腺功能亢进症 (PHPT)。甲状旁腺肿瘤有一个基质成分，特别是在非典型腺瘤和癌性病变中表现明显。最近，关于甲状旁腺肿瘤微环境 (TME) 的特征和功能的数据已经积累起来。甲状旁腺 TME 包括异质性细胞：内皮细胞、肌成纤维细胞、淋巴细胞和巨噬细胞，已经鉴定出间充质干细胞，它们中的每一个都表现出与肿瘤相关的细胞一致的表型。甲状旁腺肿瘤过度表达促血管生成分子，包括血管内皮生长因子 (VEGF-A)、成纤维细胞生长因子-2 (FGF-2) 和血管生成素，它们促进内皮细胞前体的募集和增殖，从而导致微血管密度高于正常甲状旁腺中的微血管密度。此外，甲状旁腺肿瘤内分泌细胞与基质细胞进行多方面的相互作用，部分由 CXCL12/CXCR4 途径介导，而目前，甲状旁腺肿瘤的免疫景观才刚刚开始被研究。关于甲状旁腺瘤 TME 的研究提供了 TME 在良性肿瘤中作用的一个例子，其分子机制和功能理解还很有限。
