Human Thyroid Cancers Preclinical and Translational Research Program, Division of Experimental Pathology, Cancer Research Institute, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Center for Vascular Biology Research (CVBR), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Adv Exp Med Biol. 2021;1329:253-269. doi: 10.1007/978-3-030-73119-9_14.
Thyroid cancer is the most common endocrine malignancy, and aggressive radioactive iodine refractory thyroid carcinomas still lack an effective treatment. A deeper understanding of tumor heterogeneity and microenvironment will be critical to establishing new therapeutic approaches. One of the important influencing factors of tumor heterogeneity is the diversity of cells in the tumor microenvironment. Among these are pericytes, which play an important role in blood vessel stability and angiogenesis, as well as tumor growth and metastasis. Pericytes also have stem cell-like properties and are a heterogeneous cell population, and their lineage, which has been challenging to define, may impact tumor resistance at different tumor stages. Pericytes are also important stroma cell types in the angiogenic microenvironment which express tyrosine-kinase (TK) pathways (e.g., PDGFR-β). Although TK inhibitors (TKI) and BRAF inhibitors are currently used in the clinic for thyroid cancer, their efficacy is not durable and drug resistance often develops. Characterizing the range of distinct pericyte populations and distinguishing them from other perivascular cell types may enable the identification of their specific functions in the thyroid carcinoma vasculature. This remains an essential step in developing new therapeutic strategies. Also, assessing whether thyroid tumors hold immature and/or mature vasculature with pericyte populations coverage may be key to predicting tumor response to either targeted or anti-angiogenesis therapies. It is also critical to apply different markers in order to identify pericyte populations and characterize their cell lineage. This chapter provides an overview of pericyte ontogenesis and the lineages of diverse cell populations. We also discuss the role(s) and targeting of pericytes in thyroid carcinoma, as well as their potential impact on precision targeted therapies and drug resistance.
甲状腺癌是最常见的内分泌恶性肿瘤，而侵袭性放射性碘难治性甲状腺癌仍然缺乏有效的治疗方法。深入了解肿瘤异质性和微环境对于建立新的治疗方法至关重要。肿瘤异质性的一个重要影响因素是肿瘤微环境中细胞的多样性。其中包括周细胞，它们在血管稳定性和血管生成以及肿瘤生长和转移中发挥重要作用。周细胞还具有干细胞样特性，是一种异质性细胞群体，其谱系一直难以定义，可能会影响不同肿瘤阶段的肿瘤耐药性。周细胞也是血管生成微环境中重要的间质细胞类型，表达酪氨酸激酶 (TK) 途径（如 PDGFR-β）。尽管 TK 抑制剂 (TKI) 和 BRAF 抑制剂目前在临床上用于治疗甲状腺癌，但它们的疗效并不持久，而且经常会产生耐药性。描述不同周细胞群体的范围并将其与其他血管周细胞类型区分开来，可能有助于确定它们在甲状腺癌血管中的特定功能。这仍然是开发新治疗策略的重要步骤。此外，评估甲状腺肿瘤是否具有周细胞群体覆盖的不成熟和/或成熟血管可能是预测肿瘤对靶向或抗血管生成治疗反应的关键。应用不同的标志物来识别周细胞群体并描述其细胞谱系也至关重要。本章概述了周细胞的发生和不同细胞群体的谱系。我们还讨论了周细胞在甲状腺癌中的作用和靶向作用，以及它们对精准靶向治疗和耐药性的潜在影响。
