Heterogeneity of cancer-associated fibroblasts in esophageal cancer and targeted therapy

Xu Xinyao, Zhao Lina, Lu Jiayu, Zhang Xuxu, Zheng Chunlong, Li Jiahe, Li Wei, Lu Qiang

PDF(1436 KB)
PDF(1436 KB)
Journal of Chongqing Medical University ›› 2024, Vol. 49 ›› Issue (12) : 1550-1555. DOI: 10.13406/j.cnki.cyxb.003684
Review

Heterogeneity of cancer-associated fibroblasts in esophageal cancer and targeted therapy

Author information +
History +

Abstract

Esophageal cancer(EC) is a highly invasive malignant tumor characterized by late identification,a high recurrence rate,and poor prognosis. The progression of EC is closely associated with the tumor microenvironment(TME). Cancer-associated fibroblasts(CAFs),as a key component of the TME,are recruited and reprogrammed in response to cancer cell secretions,cell contact signals,mechanical stress,and physiological stress,thereby exhibiting heterogeneity. Currently,the heterogeneity of CAFs suggests the need to develop targeted therapeutic approaches to overcome the complexity of the TME and treatment resistance. Future research will focus on a deeper understanding of the heterogeneity of CAFs and how to translate this knowledge into the advantages of clinical treatment. New treatment strategies can be designed by identifying and functionally manipulating the specific subgroups of CAFs. To clarify the complexity of CAFs in EC and their potential as therapeutic targets,this article summarizes the recent research advances in the origin and heterogeneity of CAFs and the role of CAFs in targeted therapy.

Key words

esophageal cancer / cancer-associated fibroblasts / heterogeneity / chemotherapy

Cite this article

Download Citations
Xu Xinyao , Zhao Lina , Lu Jiayu , et al . Heterogeneity of cancer-associated fibroblasts in esophageal cancer and targeted therapy. Journal of Chongqing Medical University. 2024, 49(12): 1550-1555 https://doi.org/10.13406/j.cnki.cyxb.003684

References

1
Zhu HC Ma X Ye T,et al. Esophageal cancer in China:Practice and research in the new era[J]. Int J Cancer2023152(9):1741-1751.
2
王建强,邱爱燕,张海文,等. 基质金属蛋白酶抑制剂对人胰腺癌细胞迁移和侵袭的抑制作用[J]. 现代肿瘤医学202331(22):4153-4157.
Wang JQ Qiu AY Zhang HW,et al. Anti-migration and invasion effect of matrix metalloproteinase inhibitor in human pan-creatic cancer cells[J]. J Mod Oncol202331(22):4153-4157.
3
de Visser KE Joyce JA. The evolving tumor microenvironment:From cancer initiation to metastatic outgrowth[J]. Cancer Cell202341(3):374-403.
4
Mao XQ Xu J Wang W,et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment:new findings and future perspectives[J]. Mol Cancer202120(1):131.
5
Chhabra Y Weeraratna AT. Fibroblasts in cancer:Unity in heterogeneity[J]. Cell2023186(8):1580-1609.
6
Niu NN Shen XQ Wang Z,et al. Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer[J]. Cancer Cell202442(5):869-884.
7
Luo H Xia XY Huang LB,et al. Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment[J]. Nat Commun202213(1):6619.
8
Dzobo K Dandara C. Architecture of cancer-associated fibroblasts in tumor microenvironment:mapping their origins,heterogeneity,and role in cancer therapy resistance[J]. OMICS202024(6):314-339.
9
Kennel KB Bozlar M De Valk AF,et al. Cancer-associated fibroblasts in inflammation and antitumor immunity[J]. Clin Cancer Res202329(6):1009-1016.
10
Chen YM Zhu SH Liu TY,et al. Epithelial cells activate fibroblasts to promote esophageal cancer development[J]. Cancer Cell202341(5):903-918.
11
Fang LL Che Y Zhang CQ,et al. LAMC1 upregulation via TGFβ induces inflammatory cancer-associated fibroblasts in esophageal squamous cell carcinoma via NF-κB-CXCL1-STAT3[J]. Mol Oncol202115(11):3125-3146.
12
Fang LL Che Y Zhang CQ,et al. PLAU directs conversion of fibroblasts to inflammatory cancer-associated fibroblasts,promoting esophageal squamous cell carcinoma progression via uPAR/Akt/NF-κB/IL8 pathway[J]. Cell Death Discov20217(1):32.
13
Chen J Wang Y Zhang WM,et al. Membranous NOX5-derived ROS oxidizes and activates local Src to promote malignancy of tumor cells[J]. Signal Transduct Target Ther20205(1):139.
14
Chen J Wang Y Zhang WM,et al. NOX5 mediates the crosstalk between tumor cells and cancer-associated fibroblasts via regulating cytokine network[J]. Clin Transl Med202111(8):e472.
15
Nouraee N van Roosbroeck K Vasei M,et al. Expression,tissue distribution and function of miR-21 in esophageal squamous cell carcinoma[J]. PLoS One20138(9):e73009.
16
Qiu HB Zhang X Qi JL,et al. Identification and characterization of FGFR2+ hematopoietic stem cell-derived fibrocytes as precursors of cancer-associated fibroblasts induced by esophageal squamous cell carcinoma[J]. J Exp Clin Cancer Res202241(1):240.
17
Liu XY Liu YB Xu JC,et al. Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma[J]. Clin Transl Med202313(3):e1203.
18
Jia YX Zhang BF Zhang CY,et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in esophageal squamous cell carcinoma[J]. Adv Sci202310(7):e2204565.
19
Dinh HQ Pan F Wang G,et al. Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment[J]. Nat Commun202112(1):7335.
20
Lee YE Go GY Koh EY,et al. Synergistic therapeutic combination with a CAF inhibitor enhances CAR-NK-mediated cytotoxicity via reduction of CAF-released IL-6[J]. J Immunother Cancer202311(2):e006130.
21
Xu WW Li B Guan XY,et al. Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression[J]. Nat Commun20178:14399.
22
曾瑞琪,何卫阳,曾铁兵,等. 肿瘤相关成纤维细胞的促瘤作用及其靶向治疗研究进展[J]. 现代肿瘤医学202432(16):3156-3160.
Zeng RQ He WY Zeng TB,et al. Research progress on the tumor-promoting effects of cancer-associated fibroblasts and their targeted therapy[J]. J Mod Oncol202432(16):3156-3160.
23
Jin Y Meng QL Zhang BH,et al. Cancer-associated fibroblasts-derived exosomal miR-3656 promotes the development and progression of esophageal squamous cell carcinoma via the ACAP2/PI3K-AKT signaling pathway[J]. Int J Biol Sci202117(14):3689-3701.
24
Shimizu M Koma YI Sakamoto H,et al. Metallothionein 2A expression in cancer-associated fibroblasts and cancer cells promotes esophageal squamous cell carcinoma progression[J]. Cancers202113(18):4552.
25
Kashima H Noma K Ohara T,et al. Cancer-associated fibroblasts(CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma[J]. Int J Cancer2019144(4):828-840.
26
Chen C Yang CB Tian XY,et al. Downregulation of miR-100-5p in cancer-associated fibroblast-derived exosomes facilitates lymphangiogenesis in esophageal squamous cell carcinoma[J]. Cancer Med202312(13):14468-14483.
27
Tian BQ Chen XJ Zhang HH,et al. Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma[J]. Oncotarget20178(26):42300-42313.
28
Higashino N Koma YI Hosono M,et al. Fibroblast activation protein-positive fibroblasts promote tumor progression through secretion of CCL2 and interleukin-6 in esophageal squamous cell carcinoma[J]. Lab Invest201999(6):777-792.
29
Miyako S Koma YI Nakanishi T,et al. Periostin in cancer-associated fibroblasts promotes esophageal squamous cell carcinoma progression by enhancing cancer and stromal cell migration[J]. Am J Pathol2024194(5):828-848.
30
Huang TX Tan XY Huang HS,et al. Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity[J]. Gut202271(2):333-344.
31
Liu BL Zhang BF Qi JL,et al. Targeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma[J]. Proc Natl Acad Sci U S A2023120(42):e2307914120.
32
Chu YY Fang Y Wu HT,et al. Vocal fold fibroblasts promote angiogenesis in vocal fold leukoplakia by secreting pro-angiogenic factors[J]. Auris Nasus Larynx202249(6):1009-1018.
33
Du XL Xu QP Pan DY,et al. HIC-5 in cancer-associated fibroblasts contributes to esophageal squamous cell carcinoma progression[J]. Cell Death Dis201910(12):873.
34
Croft W Evans RPT Pearce H,et al. The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy[J]. Mol Cancer202221(1):200.
35
Chen XJ Cheng GY Zhu L,et al. Alarmin S100A8 imparts chemoresistance of esophageal cancer by reprogramming cancer-associated fibroblasts[J]. Cell Rep Med20245(6):101576.
36
Zhao QT Huang L Qin GH,et al. Cancer-associated fibroblasts induce monocytic myeloid-derived suppressor cell generation via IL-6/exosomal miR-21-activated STAT3 signaling to promote cisplatin resistance in esophageal squamous cell carcinoma[J]. Cancer Lett2021518:35-48.
37
郑 雨,马 磊,李睿智,等. 细胞外基质硬度对人前列腺癌细胞可塑性调控作用的研究[J]. 精准医学杂志202439(3):222-225,231.
Zheng Y Ma L Li RZ,et al. Effect of extracellular matrix hardness on plasticity of human prostate cancer cells[J]. J Precis Med202439(3):222-225,231.
38
Yang XY Chen XJ Zhang SS,et al. Collagen 1-mediated CXCL1 secretion in tumor cells activates fibroblasts to promote radioresistance of esophageal cancer[J]. Cell Rep202342(10):113270.
39
邢思远,樊青霞,单争争,等. 食管癌免疫耐受及治疗方法的探索[J]. 肿瘤防治研究202350(12):1174-1179.
Xing SY Fan QX Shan ZZ,et al. Exploration of immune tolerance and treatment for esophageal cancer[J]. Cancer Res Prev Treat202350(12):1174-1179.
40
Li F Xin J Shi Q,et al.Advances in near infrared photoimmunotherapy of tumor[J].Journal of China Pharmaceutical University202051(6):664-674.
41
Watanabe S Noma K Ohara T,et al. Photoimmunotherapy for cancer-associated fibroblasts targeting fibroblast activation protein in human esophageal squamous cell carcinoma[J]. Cancer Biol Ther201920(9):1234-1248.
42
Katsube R Noma K Ohara T,et al. Fibroblast activation protein targeted near infrared photoimmunotherapy(NIR PIT) overcomes therapeutic resistance in human esophageal cancer. Sci Rep202111(1):1693.
43
Sato H Noma K Ohara T,et al. Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment[J]. Sci Rep202212(1):20152.

Comments

PDF(1436 KB)

Accesses

Citation

Detail

Sections
Recommended

/