Cancer-Associated Fibroblasts in Gastrointestinal Cancers: Unveiling Their Dynamic Roles in the Tumor Microenvironment

Al-Bzour, Noor N.; Al-Bzour, Ayah N.; Ababneh, Obada E.; Al-Jezawi, Moayad M.; Saeed, Azhar; Saeed, Anwaar

doi:10.3390/ijms242216505

Cited by 5 publications

(2 citation statements)

References 112 publications

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“…Importantly, studying rare diseases often results in better understanding of common disorders, and therapies against rare conditions may also be useful in a wider context (Gahl, 2012). As the tumor microenvironment including cancer-associated fibroblasts are known to play an important role in sporadic GI cancer (Al-Bzour et al, 2023), it will be interesting to address whether our findings bear relevance also beyond PJS.…”

Section: Discussionmentioning

confidence: 99%

Identification of a targetable ST2-expressing fibroblast subset driving Peutz-Jeghers syndrome polyposis

Domènech-Moreno,

Lim,

Brandt

et al. 2023

Preprint

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Inactivating germline mutations in the tumor suppressor kinaseLKB1(STK11) predispose to Peutz-Jeghers Syndrome (PJS) with increased cancer risk and early-onset development of gastrointestinal polyps requiring regular surveillance. Studies using PJS mouse models have indicated fibroblasts as drivers of polyp formation. Here, we use single-cell RNA sequencing to investigate the fibroblast heterogeneity and tumorigenic mechanisms in a PJS mouse model. We identify five distinct gastric fibroblast subsets, including a polyp-enriched ST2 (Il1rl1)-expressing crypt top fibroblast (CTF) cluster, and show that the polyps arise fromFoxl1-expressing CTFs. The transcriptional signature of the ST2+fibroblasts overlapped with the effects seen by LKB1 lossin vitroandin vivo. The ST2+fibroblasts also shared similarities with inflammation-associated fibroblasts, and inflammation exacerbated polyposis. Interestingly, the tumorigenic ST2+fibroblasts showed a distinct signaling pattern, including high expression of interleukin 11 (IL-11). Notably, IL-11 was required for the LKB1 loss-induced transcriptional changes in fibroblasts, and treatment with an IL-11 neutralizing antibody substantially reduced the tumor burden in the PJS mouse model, suggesting therapeutic value. In summary, our study uncovers a critical mechanism underlying PJS polyposis and suggests that PJS patients could benefit from anti-IL-11 therapy.

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Section: Discussionmentioning

confidence: 99%

Identification of a targetable ST2-expressing fibroblast subset driving Peutz-Jeghers syndrome polyposis

Domènech-Moreno,

Lim,

Brandt

et al. 2023

Preprint

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show abstract

“…CAFs are significant components of the tumor stroma and are primarily distributed in the perivascular or tumor peripheral fibrous mesenchyme ( 28 , 29 ). CAFs produce cytokines, ECM components, and associated enzymes ( 30 , 31 ). The ECM offers structural support to TME cells and plays a crucial role in cellular adhesion and infiltration ( 32 , 33 ).…”

Section: Overview Of the Tmementioning

confidence: 99%

Recent advances in understanding the immune microenvironment in ovarian cancer

Chen,

Yang,

et al. 2024

Front. Immunol.

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The occurrence of ovarian cancer (OC) is a major factor in women’s mortality rates. Despite progress in medical treatments, like new drugs targeting homologous recombination deficiency, survival rates for OC patients are still not ideal. The tumor microenvironment (TME) includes cancer cells, fibroblasts linked to cancer (CAFs), immune-inflammatory cells, and the substances these cells secrete, along with non-cellular components in the extracellular matrix (ECM). First, the TME mainly plays a role in inhibiting tumor growth and protecting normal cell survival. As tumors progress, the TME gradually becomes a place to promote tumor cell progression. Immune cells in the TME have attracted much attention as targets for immunotherapy. Immune checkpoint inhibitor (ICI) therapy has the potential to regulate the TME, suppressing factors that facilitate tumor advancement, reactivating immune cells, managing tumor growth, and extending the survival of patients with advanced cancer. This review presents an outline of current studies on the distinct cellular elements within the OC TME, detailing their main functions and possible signaling pathways. Additionally, we examine immunotherapy rechallenge in OC, with a specific emphasis on the biological reasons behind resistance to ICIs.

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Cancer-associated fibroblast-derived exosome Leptin promotes malignant biological lineage in pancreatic ductal adenocarcinoma by regulating ABL2 via miR-224-3p

Zhang,

Chen,

Dai

et al. 2024

Mol Biol Rep

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Cancer-Associated Fibroblasts in Gastrointestinal Cancers: Unveiling Their Dynamic Roles in the Tumor Microenvironment

Cited by 5 publications

References 112 publications

Identification of a targetable ST2-expressing fibroblast subset driving Peutz-Jeghers syndrome polyposis

Identification of a targetable ST2-expressing fibroblast subset driving Peutz-Jeghers syndrome polyposis

Recent advances in understanding the immune microenvironment in ovarian cancer

Cancer-associated fibroblast-derived exosome Leptin promotes malignant biological lineage in pancreatic ductal adenocarcinoma by regulating ABL2 via miR-224-3p

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