外科理论与实践

外科理论与实践 >

2026 , Vol. 31 >Issue 02: 158 - 162

DOI: https://doi.org/10.16139/j.1007-9610.2026.02.10

综述

肿瘤相关成纤维细胞在甲状腺癌中的研究进展

  • 刘金跃 综述 ,
  • 邱伟华 审校
展开
  • 上海交通大学医学院附属瑞金医院普外科， 上海 200025
作者贡献/Authors’ contributions

刘金跃负责文献查阅及总结、撰写；邱伟华负责指导及审校。所有作者均阅读并确认最终稿。

邱伟华，E-mail：qwh11072@rjh.com.cn

收稿日期: 2025-03-19

  网络出版日期: 2026-06-23

收起

Advance in cancer-associated fibroblasts in thyroid cancer

  • LIU Jinyue ,
  • QIU Weihua
Expand
  • Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received date: 2025-03-19

  Online published: 2026-06-23

Fold

摘要

甲状腺癌是近年来发病率上升较快的恶性肿瘤之一。肿瘤微环境在癌症发生发展过程中起到重要作用。肿瘤相关成纤维细胞（CAF）是肿瘤微环境的重要组成成分。本文阐述甲状腺癌中CAF的来源、标志物和亚群，以及CAF直接或通过重塑细胞外基质（ECM）促进甲状腺癌发展的两种机制，探讨CAF在甲状腺癌治疗中的潜在靶点，包括阻断癌细胞与CAF之间的相互作用和靶向CAF分泌因子。

关键词： 肿瘤相关成纤维细胞; 甲状腺癌; 肿瘤微环境; 细胞外基质

本文引用格式

刘金跃 综述 , 邱伟华 审校 . 肿瘤相关成纤维细胞在甲状腺癌中的研究进展[J]. 外科理论与实践, 2026 , 31(02) : 158 -162 . DOI: 10.16139/j.1007-9610.2026.02.10

Abstract

Thyroid cancer is one of the most rapidly increasing malignant tumors in recent years. Tumor microenvironment plays an important role in the occurrence and development of cancer. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment. We summarized the origins, biomarkers, and subpopulations of CAF in thyroid cancer, as well as the two mechanisms by which CAFs promote thyroid cancer either directly or by remodeling the extracellular matrix (ECM). Finally, potential targets of CAF for treating thyroid cancer were discussed, including blocking the interaction between cancer cells and CAF, and targeting CAF-secreted factors.

Key words： Cancer-associated fibroblast(CAF); Thyroid cancer; Tumor microenvironment(TME); Extracellular matrix(ECM)

参考文献

[1] SIEGEL R L, MILLER K D, WAGLE N S, et al. Cancer statistics,2023[J]. CA Cancer J Clin, 2023, 73(1):17-48.
[2] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
[3] MILLER K D, NOGUEIRA L, DEVASIA T, et al. Cancer treatment and survivorship statistics,2022[J]. CA Cancer J Clin, 2022, 72(5):409-436.
[4] SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics,2022[J]. CA Cancer J Clin, 2022, 72(1):7-33.
[5] BOGENRIEDER T, HERLYN M. Axis of evil: molecular mechanisms of cancer metastasis[J]. Oncogene, 2003, 22(42):6524-6536.
[6] XIAO Y, YU D. Tumor microenvironment as a therapeutic target in cancer[J]. Pharmacol Ther, 2021,221:107753.
[7] JIN Z, LU Y, WU X, et al. The cross-talk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer[J]. Redox Biol, 2021,46:102076.
[8] WANG D, WANG X, SONG Y, et al. Exosomal miR-146a-5p and miR-155-5p promote CXCL12/CXCR7-induced metastasis of colorectal cancer by crosstalk with cancer-associated fibroblasts[J]. Cell Death Dis, 2022, 13(4):380.
[9] WEN S, HOU Y, FU L, et al. Cancer-associated fibroblast (CAF)-derived IL32 promotes breast cancer cell invasion and metastasis via integrin beta3-p38 MAPK signalling[J]. Cancer Lett, 2019,442:320-332.
[10] XU H, ZHAO J, LI J, et al. Cancer associated fibroblast-derived CCL5 promotes hepatocellular carcinoma metastasis through activating HIF1alpha/ZEB1 axis[J]. Cell Death Dis, 2022, 13(5):478.
[11] SUN X, HE X, ZHANG Y, et al. Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism[J]. Gut, 2022, 71(1):129-147.
[12] SHIN E, KOO J S. Cell component and function of tumor microenvironment in thyroid cancer[J]. Int J Mol Sci, 2022, 23(20):12578.
[13] GUARINO V, CASTELLONE M D, AVILLA E, et al. Thyroid cancer and inflammation[J]. Mol Cell Endocrinol, 2010, 321(1):94-102.
[14] MUZZA M, DEGL'INNOCENTI D, COLOMBO C, et al. The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies[J]. Clin Endocrinol(Oxf), 2010, 72(5):702-708.
[15] CHEN Y, MCANDREWS K M, KALLURI R. Clinical and therapeutic relevance of cancer-associated fibroblasts[J]. Nat Rev Clin Oncol, 2021, 18(12):792-804.
[16] SAHAI E, ASTSATUROV I, CUKIERMAN E, et al. A framework for advancing our understanding of cancer-associated fibroblasts[J]. Nat Rev Cancer, 2020, 20(3):174-186.
[17] DRISKELL R R, LICHTENBERGER B M, HOSTE E, et al. Distinct fibroblast lineages determine dermal architecture in skin development and repair[J]. Nature, 2013, 504(7479):277-281.
[18] KALLURI R. The biology and function of fibroblasts in cancer[J]. Nat Rev Cancer, 2016, 16(9):582-598.
[19] DVORAK H F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing[J]. N Engl J Med, 1986, 315(26):1650-1659.
[20] ROSS R, RAINES E W, BOWEN-POPE D F. The biology of platelet-derived growth factor[J]. Cell, 1986, 46(2):155-169.
[21] RAZ Y, COHEN N, SHANI O, et al. Bone marrow-derived fibroblasts are a functionally distinct stromal cell population in breast cancer[J]. J Exp Med, 2018, 215(12):3075-3093.
[22] ZEISBERG E M, POTENTA S, XIE L, et al. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts[J]. Cancer Res, 2007, 67(21):10123-10128.
[23] BOCHET L, LEHUEDE C, DAUVILLIER S, et al. Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer[J]. Cancer Res, 2013, 73(18):5657-5668.
[24] APTE M V, HABER P S, DARBY S J, et al. Pancreatic stellate cells are activated by proinflammatory cytokines:implications for pancreatic fibrogenesis[J]. Gut, 1999, 44(4):534-541.
[25] YIN C, EVASON K J, ASAHINA K, et al. Hepatic stellate cells in liver development, regeneration, and cancer[J]. J Clin Invest, 2013, 123(5):1902-1910.
[26] JOLLY L A, NOVITSKIY S, OWENS P, et al. Fibroblast-mediated collagen remodeling within the tumor microenvironment facilitates progression of thyroid cancers driven by brafv600e and pten loss[J]. Cancer Res, 2016, 76(7):1804-1813.
[27] WEN S, QU N, MA B, et al. Cancer-associated fibroblasts positively correlate with dedifferentiation and aggressiveness of thyroid cancer[J]. Onco Targets Ther, 2021,14:1205-1217.
[28] FOZZATTI L, ALAMINO V A, PARK S, et al. Interplay of fibroblasts with anaplastic tumor cells promotes follicular thyroid cancer progression[J]. Sci Rep, 2019, 9(1):8028.
[29] ZHANG J, WANG Y, LI D, et al. Notch and TGF-beta/Smad3 pathways are involved in the interaction between cancer cells and cancer-associated fibroblasts in papillary thyroid carcinoma[J]. Tumour Biol, 2014, 35(1):379-385.
[30] ELYADA E, BOLISETTY M, LAISE P, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts[J]. Cancer Discov, 2019, 9(8):1102-1123.
[31] YAN T, QIU W, WENG H, et al. Single-cell transcriptomic analysis of ecosystems in papillary thyroid carcinoma progression[J]. Front Endocrinol (Lausanne), 2021,12:729565.
[32] CHEN S, ZHU G, YANG Y, et al. Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression[J]. Nat Cell Biol, 2021, 23(1):87-98.
[33] BARTOSCHEK M, OSKOLKOV N, BOCCI M, et al. Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing[J]. Nat Commun, 2018, 9(1):5150.
[34] CHO J G, BYEON H K, OH K H, et al. Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis[J]. Eur Arch Otorhinolaryngol, 2018, 275(9):2355-2361.
[35] SAITOH O, MITSUTAKE N, NAKAYAMA T, et al. Fibroblast-mediated in vivo and in vitro growth promotion of tumorigenic rat thyroid carcinoma cells but not normal Fisher rat thyroid follicular cells[J]. Thyroid, 2009, 19(7):735-742.
[36] HUANG C, YANG X, HAN L, et al. The prognostic potential of alpha-1 type Ⅰ collagen expression in papillary thyroid cancer[J]. Biochem Biophys Res Commun, 2019, 515(1):125-132.
[37] BOUFRAQECH M, PATEL D, NILUBOL N, et al. Lysyl oxidase is a key player in BRAF/MAPK pathway-driven thyroid cancer aggressiveness[J]. Thyroid, 2019, 29(1):79-92.
[38] MINNA E, BRICH S, TODOERTI K, et al. Cancer associated fibroblasts and senescent thyroid cells in the invasive front of thyroid carcinoma[J]. Cancers (Basel), 2020, 12(1):112.
[39] PAN Z, XU T, BAO L, et al. CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment[J]. Mol Cancer, 2022, 21(1):190.
[40] BIBLE K C, KEBEBEW E, BRIERLEY J, et al. 2021 american thyroid association guidelines for management of patients with anaplastic thyroid cancer[J]. Thyroid,2021, 31(3):337-386.
[41] SUN W, XU Y, ZHAO C, et al. Targeting TGF-beta1 suppresses survival of and invasion by anaplastic thyroid carcinoma cells[J]. Am J Transl Res, 2017, 9(3):1418-1425.
[42] SHIRLEY L A, MCCARTY S, YANG M C, et al. Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target[J]. Surgery, 2016, 159(1):163-170.
[43] YOUNES M N, KIM S, YIGITBASI O G, et al. Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer[J]. Mol Cancer Ther, 2005, 4(8):1146-1156.
[44] CAO X, HE Q. Ursolic acid inhibits proliferation, migration and invasion of human papillary thyroid carcinoma cells via CXCL12/CXCR4/CXCR7 axis through cancer-associated fibroblasts[J]. Hum Exp Toxicol, 2022,41:774837723.
[45] ECKERT F, SCHILBACH K, KLUMPP L, et al. Potential role of CXCR4 targeting in the context of radiotherapy and immunotherapy of cancer[J]. Front Immunol, 2018,9:3018.
[46] FEIG C, JONES J O, KRAMAN M, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer[J]. Proc Natl Acad Sci U S A, 2013, 110(50):20212-20217.
[47] WU Z, CAO Y, JIANG X, et al. Clinicopathological significance of chemokine receptor CXCR4 expression in papillary thyroid carcinoma: a meta-analysis[J]. Minerva Endocrinol, 2020, 45(1):43-48.
[48] LIN Y, MA Q, LI L, et al. The CXCL12-CXCR4 axis promotes migration, invasiveness, and EMT in human papillary thyroid carcinoma B-CPAP cells via NF-kappaB signaling[J]. Biochem Cell Biol, 2018, 96(5):619-626.
[49] LIU Z, YANG L, TENG X, et al. The involvement of CXCR7 in modulating the progression of papillary thyroid carcinoma[J]. J Surg Res, 2014, 191(2):379-388.
[50] JUNG Y H, LEE D Y, CHA W, et al. Antitumor effect of CXCR4 antagonist AMD3100 on the tumorigenic cell line of BHP10-3 papillary thyroid cancer cells[J]. Head Neck, 2016, 38(10):1479-1486.
[51] ZHOU J, XU M, TAN J, et al. MMP1 acts as a potential regulator of tumor progression and dedifferentiation in papillary thyroid cancer[J]. Front Oncol, 2022,12:1030590.
[52] ZHANG K, LIU X, HAO F, et al. Targeting TGF-beta1 inhibits invasion of anaplastic thyroid carcinoma cell through SMAD2-dependent S100A4-MMP-2/9 signalling[J]. Am J Transl Res, 2016, 8(5):2196-2209.
[53] SHE M, JIM Y S. Combining a matrix metalloproteinase inhibitor, a farnesyltransferase inhibitor, and a taxane improves survival in an anaplastic thyroid cancer model[J]. Cancer Lett, 2006, 238(2):197-201.
Options
文章导航

/

〈 〉