Cancer‑associated fibroblast regulation of tumor neo‑angiogenesis as a therapeutic target in cancer (Review)

Wang, Fang‐Tao; Sun, Wei; Zhang, Jingtao; Fan, Yonggang

doi:10.3892/ol.2019.9973

Cited by 87 publications

(73 citation statements)

References 134 publications

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“…CAFs produce ECM proteins, which prompts immunosuppression of tumor cells by recruiting immunosuppressive cells [64,65] such as monocytes and inducing immunosuppressive PD-1+ TAMs, as recently shown in breast cancer cells in vitro [66]. In addition, CAFs promote angiogenesis by producing fibroblast growth factor 2 (FGF2), and vascular endothelial growth factor A (VEGFA) in different cancers [67] as well as galectin-1 expression in gastric cancer [68].…”

Section: Cancer-associated Fibroblast (Cafs)mentioning

confidence: 88%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

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Section: Cancer-associated Fibroblast (Cafs)mentioning

confidence: 88%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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“…Tumor growth depends to a large extent on the metabolism of cancer cells [119]. The disordered distribution of tumor blood vessels and the loss of normal vascular function lead to local hypoxia and impaired nutrient supplies.…”

Section: Promoting Angiogenesis To Enhance Proliferation and Migrationmentioning

confidence: 99%

Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

125

117

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Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

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“…CAFs, as the most critical stromal cells in TME, participate in the process of tumor growth and development [6][7][8][9][10][11]39]. As an important supplement to tumor microcirculation, VM occurs in certain highly aggressive malignancies, and is closely related to tumor progression and poor prognosis [13][14][15][16]40].…”

Section: Discussionmentioning

confidence: 99%

“…Tumor microenvironment (TME), also known as tumor stroma, is composed of extracellular matrix (ECM) and a variety of stromal cells [4][5]. Cancer-associated broblasts (CAFs) are the most important stromal cells in TME, which play an important role in tumor growth and development, and participate in many biological processes such as tumor proliferation, invasion and metastasis, angiogenesis [6][7][8][9][10], and are related to poor prognosis [11]. In these biological processes, angiogenesis and effective blood supply are the basic conditions for tumor growth and metastasis [12].…”

Section: Introductionmentioning

confidence: 99%

Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth of gallbladder cancers via upregulating the expression of NOX4, a poor prognosis factor, through activating IL-6-JAK-STAT3 signal pathway

Pan

Wang

Ansari

et al. 2020

Preprint

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Background Cancer-associated fibroblasts (CAFs) and vasculogenic mimicry (VM) play important roles in the occurrence and development of tumors. However, the relationship between CAFs and VM formation, especially in gallbladder cancer (GBC) has not been clarified. In this study, we investigated whether gallbladder CAFs (GCAFs) can promote VM formation and tumor growth and explored the underlying molecular mechanism.Methods A co-culture system of human GBC cells and fibroblasts or HUVECs was established. VM formation, proliferation, invasion, migration, tube formation assays, CD31-PAS double staining, optic/electron microscopy and tumor xenograft assay were used to detect VM formation and malignant phenotypes of 3-D co-culture matrices in vitro, as well as the VM formation and tumor growth of xenografts in vivo, respectively. Microarray analysis was used to analyze gene expression profile in GCAFs/NFs and VM (+)/VM (-) in vitro. QRT-PCR, western blotting, IHC and CIF were used to detected NOX4 expression in GCAFs/NFs, 3-D culture/co-culture matrices in vitro, the xenografts in vivo and human gallbladder tissue/stroma samples. The correlation between NOX4 expression and clinicopathological and prognostic factors of GBC patients was analyzed. And, the underlying molecular mechanism of GCAFs promoting VM formation and tumor growth in GBC was explored.Results GCAFs promote VM formation and tumor growth in GBC; and the finding was confirmed by facts that GCAFs induced proliferation, invasion, migration and tube formation of GBC cells in vitro, and promoted VM formation and tumor growth of xenografts in vivo. NOX4 is highly expressed in GBC and its stroma, which is the key gene for VM formation, and is correlated with tumor aggression and survival of GBC patients. The GBC patients with high NOX4 expression in tumor cells and stroma have a poor prognosis. The underlying molecular mechanism may be related to the up-regulation of NOX4 expression through paracrine IL-6 mediated IL-6/JAK/STAT3 signaling pathway.Conclusions GCAFs promote VM formation and tumor growth in GBC via upregulating NOX4 expression through the activation of IL-6-JAK-STAT3 signal pathway. NOX4, as a VM-related gene in GBC, is over-expressed in GBC cells and GCAFs, which is related to aggression and unfavorable prognosis of GBC patients.

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Cancer‑associated fibroblast regulation of tumor neo‑angiogenesis as a therapeutic target in cancer (Review)

Cited by 87 publications

References 134 publications

Tumor microenvironment complexity and therapeutic implications at a glance

Tumor microenvironment complexity and therapeutic implications at a glance

Exosomal miRNAs in tumor microenvironment

Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth of gallbladder cancers via upregulating the expression of NOX4, a poor prognosis factor, through activating IL-6-JAK-STAT3 signal pathway

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