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Role of Cancer-Associated Fibroblasts in the Formation of the Pre-Metastatic Niche
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1. Basic Medical College Institute of Microcirculation,Hebei North University

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    Abstract:

    As the global incidence of cancer continues to rise, tumor metastasis has emerged as the leading cause of death among cancer patients. The formation of the pre-metastatic niche creates a favorable microenvironment for tumor cell colonization and metastasis, significantly driving the spread of cancer. In this context, cancer-associated fibroblasts (CAFs) have garnered significant attention for their multifaceted roles in tumor progression. CAFs contribute to the establishment of the pre-metastatic niche and enhance the invasive behavior of tumor cells by remodeling the extracellular matrix, inducing epithelial-mesenchymal transition, stimulating angiogenesis, and modulating the tumor immune microenvironment. These actions not only accelerate the metastatic process but also facilitate immune evasion by the tumor. This review delves into the pivotal mechanisms and functions of CAFs in tumor metastasis, exploring their potential applications in cancer research and therapy, and offering new perspectives for the development of anti-metastatic strategies.

    Reference
    [1] CHENG J N, YUAN Y X, ZHU B, et al. Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression [J]. Front Cell Dev Biol, 2021, 9: 740827.
    [2] JANG I, BENINGO K A. Integrins, CAFs and Mechanical Forces in the Progression of Cancer [J]. Cancers (Basel), 2019, 11(5).
    [3] RIZZOLIO S, GIORDANO S, CORSO S. The importance of being CAFs (in cancer resistance to targeted therapies) [J]. J Exp Clin Cancer Res, 2022, 41(1): 319.
    [4] TSOUMAKIDOU M. The advent of immune stimulating CAFs in cancer [J]. Nat Rev Cancer, 2023, 23(4): 258-69.
    [5] PAPAIT A, ROMOLI J, STEFANI F R, et al. Fight the Cancer, Hit the CAF! [J]. Cancers (Basel), 2022, 14(15).
    [6] WRIGHT K, LY T, KRIET M, et al. Cancer-Associated Fibroblasts: Master Tumor Microenvironment Modifiers [J]. Cancers (Basel), 2023, 15(6).
    [7] CANNONE S, GRECO M R, CARVALHO T M A, et al. Cancer Associated Fibroblast (CAF) Regulation of PDAC Parenchymal (CPC) and CSC Phenotypes Is Modulated by ECM Composition [J]. Cancers (Basel), 2022, 14(15).
    [8] LIU X, LI J, YANG X, et al. Carcinoma-associated fibroblast-derived lysyl oxidase-rich extracellular vesicles mediate collagen crosslinking and promote epithelial-mesenchymal transition via p-FAK/p-paxillin/YAP signaling [J]. Int J Oral Sci, 2023, 15(1): 32.
    [9] WINKLER J, ABISOYE-OGUNNIYAN A, METCALF K J, et al. Concepts of extracellular matrix remodelling in tumour progression and metastasis [J]. Nat Commun, 2020, 11(1): 5120.
    [10] YU C-C, KIM D K, KIM E K, et al. Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts [J]. Plos One, 2019, 14(3).
    [11] LIU T, ZHOU L, YANG K, et al. The β-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts [J]. Signal Transduction and Targeted Therapy, 2019, 4(1).
    [12] FATTET L, JUNG H-Y, MATSUMOTO M W, et al. Matrix Rigidity Controls Epithelial-Mesenchymal Plasticity and Tumor Metastasis via a Mechanoresponsive EPHA2/LYN Complex [J]. Developmental Cell, 2020, 54(3): 302-16.e7.
    [13] TAKATSU F, SUZAWA K, TOMIDA S, et al. Periostin secreted by cancer-associated fibroblasts promotes cancer progression and drug resistance in non-small cell lung cancer [J]. J Mol Med (Berl), 2023, 101(12): 1603-14.
    [14] GHOFRANI-SHAHPAR M, PAKRAVAN K, RAZMARA E, et al. Cancer-associated fibroblasts drive colorectal cancer cell progression through exosomal miR-20a-5p-mediated targeting of PTEN and stimulating interleukin-6 production [J]. BMC Cancer, 2024, 24(1): 400.
    [15] JIANG B, XIAO S, ZHANG S, et al. The miR-1290/OGN axis in ovarian cancer-associated fibroblasts modulates cancer cell proliferation and invasion [J]. J Ovarian Res, 2024, 17(1): 52.
    [16] ZHANG Y, SUN S, QI Y, et al. Characterization of tumour microenvironment reprogramming reveals invasion in epithelial ovarian carcinoma [J]. J Ovarian Res, 2023, 16(1): 200.
    [17] KUMAR D, NEW J, VISHWAKARMA V, et al. Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression [J]. Cancer Res, 2018, 78(14): 3769-82.
    [18] AWAJI M, FUTAKUCHI M, HEAVICAN T, et al. Cancer-Associated Fibroblasts Enhance Survival and Progression of the Aggressive Pancreatic Tumor Via FGF-2 and CXCL8 [J]. Cancer Microenviron, 2019, 12(1): 37-46.
    [19] BORDIGNON P, BOTTONI G, XU X, et al. Dualism of FGF and TGF-beta Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant [J]. Cell Rep, 2019, 28(9): 2358-72 e6.
    [20] CHEN J, HUANG Q, LI Y Q, et al. Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma [J]. Cell Death Dis, 2024, 15(1): 15.
    [21] SOONGSATHITANON J, JAMJUNTRA P, SUMRANSUB N, et al. Crosstalk between Tumor-Infiltrating Immune Cells and Cancer-Associated Fibroblasts in Tumor Growth and Immunosuppression of Breast Cancer [J]. J Immunol Res, 2021, 2021: 8840066.
    [22] MORI Y, OKIMOTO Y, SAKAI H, et al. Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1alpha and tumor progression of clear cell ovarian cancer [J]. Cell Rep Med, 2024, 5(5): 101532.
    [23] REN X, LI L, WU J, et al. PDGF-BB regulates the transformation of fibroblasts into cancer-associated fibroblasts via the lncRNA LURAP1L-AS1/LURAP1L/IKK/IkappaB/NF-kappaB signaling pathway [J]. Oncol Lett, 2021, 22(1): 537.
    [24] YOU D, WANG Y, XU J, et al. MiR-3529-3p from PDGF-BB-induced cancer-associated fibroblast-derived exosomes promotes the malignancy of oral squamous cell carcinoma [J]. Discov Oncol, 2023, 14(1): 166.
    [25] CADAMURO M, BRIVIO S, MERTENS J, et al. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma [J]. J Hepatol, 2019, 70(4): 700-9.
    [26] YAN J, XIAO G, YANG C, et al. Cancer-Associated Fibroblasts Promote Lymphatic Metastasis in Cholangiocarcinoma via the PDGF-BB/PDGFR-beta Mediated Paracrine Signaling Network [J]. Aging Dis, 2024, 15(1): 369-89.
    [27] ZHOU J, SCHWENK-ZIEGER S, KRANZ G, et al. Isolation and characterization of head and neck cancer-derived peritumoral and cancer-associated fibroblasts [J]. Front Oncol, 2022, 12: 984138.
    [28] GUO X, CHEN M, CAO L, et al. Cancer-Associated Fibroblasts Promote Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-101-3p Mediated VEGFA Secretion and AKT/eNOS Pathway [J]. Front Cell Dev Biol, 2021, 9: 764151.
    [29] WAN X, GUAN S, HOU Y, et al. FOSL2 promotes VEGF-independent angiogenesis by transcriptionnally activating Wnt5a in breast cancer-associated fibroblasts [J]. Theranostics, 2021, 11(10): 4975-91.
    [30] YANG Y, MA Y, YAN S, et al. CAF promotes chemoresistance through NRP2 in gastric cancer [J]. Gastric Cancer, 2022, 25(3): 503-14.
    [31] LIU Y, QU H C, HUANG Y. Renal clear cell carcinoma-derived CXCL5 drives tumor-associated fibroblast formation and facilitates cancer progression [J]. Pathol Res Pract, 2023, 244: 154319.
    [32] OSTRAND-ROSENBERG S, LAMB T J, PAWELEC G. Here, There, and Everywhere: Myeloid-Derived Suppressor Cells in Immunology [J]. J Immunol, 2023, 210(9): 1183-97.
    [33] LIANG T, TAO T, WU K, et al. Cancer-Associated Fibroblast-Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer [J]. Adv Sci (Weinh), 2023, 10(31): e2303230.
    [34] SUN R, LUO H, SU J, et al. Olaparib Suppresses MDSC Recruitment via SDF1alpha/CXCR4 Axis to Improve the Anti-tumor Efficacy of CAR-T Cells on Breast Cancer in Mice [J]. Mol Ther, 2021, 29(1): 60-74.
    [35] MONTERAN L, ERSHAID N, DORON H, et al. Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer [J]. Nat Commun, 2022, 13(1): 5797.
    [36] JIN H, KIM H J. NK Cells Lose Their Cytotoxicity Function against Cancer Stem Cell-Rich Radiotherapy-Resistant Breast Cancer Cell Populations [J]. Int J Mol Sci, 2021, 22(17).
    [37] WANG L, CAO Y, GUO W, et al. High expression of cuproptosis-related gene FDX1 in relation to good prognosis and immune cells infiltration in colon adenocarcinoma (COAD) [J]. J Cancer Res Clin Oncol, 2023, 149(1): 15-24.
    [38] VAN DEN EYNDE A, GEHRCKEN L, VERHEZEN T, et al. IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts [J]. J Hematol Oncol, 2024, 17(1): 8.
    [39] LEE Y E, GO G Y, KOH E Y, et al. Synergistic therapeutic combination with a CAF inhibitor enhances CAR-NK-mediated cytotoxicity via reduction of CAF-released IL-6 [J]. J Immunother Cancer, 2023, 11(2).
    [40] YAO L, HOU J, WU X, et al. Cancer-associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosis via iron regulation [J]. Redox Biol, 2023, 67: 102923.
    [41] PENG Z, YE M, DING H, et al. Spatial transcriptomics atlas reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment components in colorectal cancer [J]. J Transl Med, 2022, 20(1): 302.
    [42] LUAN J, LIU Y, CAO M, et al. The pathogenic response of cytotoxic T?lymphocytes, a common therapeutic target for cancer, has a direct impact on treatment outcomes (Review) [J]. Oncol Rep, 2024, 52(1).
    [43] AGORKU D J, BOSIO A, ALVES F, et al. Colorectal cancer-associated fibroblasts inhibit effector T cells via NECTIN2 signaling [J]. Cancer Lett, 2024, 595: 216985.
    [44] GORCHS L, KAIPE H. Interactions between Cancer-Associated Fibroblasts and T Cells in the Pancreatic Tumor Microenvironment and the Role of Chemokines [J]. Cancers (Basel), 2021, 13(12).
    [45] LOU M, IWATSUKI M, WU X, et al. Cancer-Associated Fibroblast-Derived IL-8 Upregulates PD-L1 Expression in Gastric Cancer Through the NF-kappaB Pathway [J]. Ann Surg Oncol, 2024, 31(5): 2983-95.
    [46] LI X, ZHAI J, SHEN Y, et al. Tumor-derived IL-8 facilitates lymph node metastasis of gastric cancer via PD-1 up-regulation in CD8(+) T cells [J]. Cancer Immunol Immunother, 2022, 71(12): 3057-70.
    [47] BLINOVA V G, ZHDANOV D D. Many Faces of Regulatory T Cells: Heterogeneity or Plasticity? [J]. Cells, 2024, 13(11).
    [48] VARVERI A, PAPADOPOULOU M, PAPADOVASILAKIS Z, et al. Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development [J]. Nat Commun, 2024, 15(1): 4988.
    [49] SUN R Z H, GAO DS, NI A, LI H, CHEN L, LU X, CHEN K, LU B. Amphiregulin couples IL1RL1+regulatory T cells and cancer-associated fibroblasts to impede antitumor immunit [J]. Sci Adv, Epub 2023 Aug 23., 9(34):eadd7399.
    [50] DONG G, CHEN P, XU Y, et al. Cancer-associated fibroblasts: Key criminals of tumor pre-metastatic niche [J]. Cancer Lett, 2023, 566: 216234.
    [51] DHUNGEL N, DRAGOI A-M. Exploring the multifaceted role of direct interaction between cancer cells and fibroblasts in cancer progression [J]. Frontiers in Molecular Biosciences, 2024, 11.
    [52] GUO T, XU J. Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy [J]. Cancer and Metastasis Reviews, 2024, 43(3): 1095-116.
    [53] GENG X, CHEN H, ZHAO L, et al. Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer [J]. Front Cell Dev Biol, 2021, 9: 655152.
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History
  • Received:September 05,2024
  • Revised:October 19,2024
  • Adopted:January 08,2025
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