外科理论与实践 ›› 2026, Vol. 31 ›› Issue (02): 158-162.doi: 10.16139/j.1007-9610.2026.02.10
收稿日期:2025-03-19
出版日期:2026-04-25
发布日期:2026-06-23
通讯作者:
邱伟华,E-mail:qwh11072@rjh.com.cn
作者简介: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。
Received:2025-03-19
Online:2026-04-25
Published:2026-06-23
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。
中图分类号:
刘金跃, 邱伟华. 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.
LIU Jinyue, QIU Weihua. Advance in cancer-associated fibroblasts in thyroid cancer[J]. Journal of Surgery Concepts & Practice, 2026, 31(02): 158-162.
| [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.
doi: 10.1038/sj.onc.1206757 pmid: 14528277 |
| [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.
doi: 10.1038/s41419-022-04825-6 pmid: 35443745 |
| [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.
doi: 10.1038/s41419-022-04935-1 |
| [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.
doi: 10.1136/gutjnl-2020-322744 pmid: 33568427 |
| [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.
doi: 10.3390/ijms232012578 URL |
| [13] |
GUARINO V, CASTELLONE M D, AVILLA E, et al. Thyroid cancer and inflammation[J]. Mol Cell Endocrinol, 2010, 321(1):94-102.
doi: 10.1016/j.mce.2009.10.003 pmid: 19835928 |
| [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.
doi: 10.1111/cen.2010.72.issue-5 URL |
| [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.
doi: 10.1038/s41571-021-00546-5 pmid: 34489603 |
| [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.
doi: 10.1038/s41568-019-0238-1 pmid: 31980749 |
| [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.
doi: 10.1038/nature12783 |
| [18] |
KALLURI R. The biology and function of fibroblasts in cancer[J]. Nat Rev Cancer, 2016, 16(9):582-598.
doi: 10.1038/nrc.2016.73 pmid: 27550820 |
| [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.
doi: 10.1056/NEJM198612253152606 URL |
| [20] |
ROSS R, RAINES E W, BOWEN-POPE D F. The biology of platelet-derived growth factor[J]. Cell, 1986, 46(2):155-169.
pmid: 3013421 |
| [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.
doi: 10.1084/jem.20180818 URL |
| [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.
doi: 10.1158/0008-5472.CAN-07-3127 pmid: 17974953 |
| [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.
doi: 10.1158/0008-5472.CAN-13-0530 pmid: 23903958 |
| [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.
doi: 10.1136/gut.44.4.534 URL |
| [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.
doi: 10.1172/JCI66369 pmid: 23635788 |
| [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.
doi: 10.1158/0008-5472.CAN-15-2351 pmid: 26818109 |
| [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.
doi: 10.1038/s41598-019-44361-6 pmid: 31142771 |
| [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.
doi: 10.1007/s13277-013-1053-z URL |
| [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.
doi: 10.1158/2159-8290.CD-19-0094 pmid: 31197017 |
| [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.
doi: 10.1038/s41556-020-00613-6 pmid: 33420488 |
| [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.
doi: 10.1038/s41467-018-07582-3 pmid: 30514914 |
| [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.
doi: 10.1007/s00405-018-5061-x |
| [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.
doi: 10.1089/thy.2009.0017 URL |
| [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.
doi: 10.1016/j.bbrc.2019.04.119 URL |
| [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.
doi: 10.1089/thy.2018.0424 pmid: 30398411 |
| [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.
doi: 10.3390/cancers12010112 URL |
| [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.
doi: 10.1186/s12943-022-01658-x pmid: 36192735 |
| [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.
doi: 10.1089/thy.2020.0944 URL |
| [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.
doi: 10.1016/j.surg.2015.10.016 URL |
| [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.
doi: 10.1158/1535-7163.MCT-05-0078 pmid: 16093430 |
| [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.
doi: 10.1073/pnas.1320318110 URL |
| [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.
doi: 10.23736/S0391-1977.18.02709-8 pmid: 29424203 |
| [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.
doi: 10.1139/bcb-2017-0074 URL |
| [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.
doi: 10.1016/j.jss.2014.04.016 pmid: 24814201 |
| [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.
doi: 10.1002/hed.v38.10 URL |
| [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.
pmid: 16154259 |
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