TGFβ Signaling Activated by Cancer-Associated Fibroblasts Determines the Histological Signature of Lung Adenocarcinoma

Sato, Ryo; Imamura, Kosuke; Semba, Takashi; Tomita, Yusuke; Saeki, Sho; Ikeda, Koei; Komohara, Yoshihiro; Suzuki, Makoto; Sakagami, Takuro; Saya, Hideyuki; Arima, Yoshimi

doi:10.1158/0008-5472.can-20-3941

Cited by 37 publications

(30 citation statements)

References 47 publications

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“…These CAFs significantly promote the infiltration of arginase+ N2 neutrophils and stimulate their expression of CXCL2, CXCR4, and MMP-9 [107]. Furthermore, it has been shown that CAFs mediate the activation of TGF-β/Smad3 signaling in tumor cells to induce IL-8 secretion and promote MPO + neutrophil migration in lung cancer [172]. These MPO + neutrophils have been reported to contribute to the tumor progression, through the support of angiogenesis.…”

Section: Mechanisms Regulating Pro-and Anti-angiogenic Activity Of Neutrophils In Cancermentioning

confidence: 96%

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The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer

Ozel

Duerig

Domnich

et al. 2022

Cancers

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Angiogenesis, the formation of new blood vessels from already existing vasculature, is tightly regulated by pro- and anti-angiogenic stimuli and occurs under both physiological and pathological conditions. Tumor angiogenesis is central for tumor development, and an “angiogenic switch” could be initiated by multiple immune cells, such as neutrophils. Tumor-associated neutrophils promote tumor angiogenesis by the release of both conventional and non-conventional pro-angiogenic factors. Therefore, neutrophil-mediated tumor angiogenesis should be taken into consideration in the design of novel anti-cancer therapy. This review recapitulates the complex role of neutrophils in tumor angiogenesis and summarizes neutrophil-derived pro-angiogenic factors and mechanisms regulating angiogenic activity of tumor-associated neutrophils. Moreover, it provides up-to-date information about neutrophil-targeting therapy, complementary to anti-angiogenic treatment.

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Section: Mechanisms Regulating Pro-and Anti-angiogenic Activity Of Neutrophils In Cancermentioning

confidence: 96%

“…These MPO + neutrophils have been reported to contribute to the tumor progression, through the support of angiogenesis. Additionally, by releasing MMP-9, these neutrophils were suggested to promote further activation of TGFβ in tumor microenvironment [172].…”

Section: Mechanisms Regulating Pro-and Anti-angiogenic Activity Of Neutrophils In Cancermentioning

confidence: 99%

The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer

Ozel

Duerig

Domnich

et al. 2022

Cancers

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show abstract

“…Sato et al showed correlation between TGFβ secretion from CAFs and tumor heterogeneity in lung adenocarcinomas. TGFβ stimulated lung adenocarcinomas tumor plasticity into acinar type [51]. Hence, TGFβ mediates a certain role in cell-to-cell cross talk between tumor and tumor microenvironments.…”

Section: Tumor Stromamentioning

confidence: 94%

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Wieleba

Wojas‐Krawczyk

Krawczyk

et al. 2022

IJMS

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Despite the enormous progress and development of modern therapies, lung cancer remains one of the most common causes of death among men and women. The key element in the development of new anti-cancer drugs is proper planning of the preclinical research phase. The most adequate basic research exemplary for cancer study are 3D tumor microenvironment in vitro models, which allow us to avoid the use of animal models and ensure replicable culture condition. However, the question tormenting the scientist is how to choose the best tool for tumor microenvironment research, especially for extremely heterogenous lung cancer cases. In the presented review we are focused to explain the key factors of lung cancer biology, its microenvironment, and clinical gaps related to different therapies. The review summarized the most important strategies for in vitro culture models mimicking the tumor–tumor microenvironmental interaction, as well as all advantages and disadvantages were depicted. This knowledge could facilitate the right decision to designate proper pre-clinical in vitro study, based on available analytical tools and technical capabilities, to obtain more reliable and personalized results for faster introduction them into the future clinical trials.

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“…In a separate study, Sato et al . showed that TGF-β1 released by α-SMA + mouse CAF induced morphological changes and gene expression of the tumor cells, thus may contribute to the histological heterogeneity of lung adenocarcinoma (Sato et al 2021 ). With regard to the effect of CAF heterogeneity on the "methylome", Su et al .…”

Section: Tumor Fibrosismentioning

confidence: 99%

Integrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?

Zeltz

Navab

Heljasvaara

et al. 2022

J. Cell Commun. Signal.

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There is currently an increased interest in understanding the role of the tumor microenvironment (TME) in tumor growth and progression. In this context the role of integrins in cancer-associated fibroblasts (CAFs) will need to be carefully re-evaluated. Fibroblast-derived cells are not only in the focus in tumors, but also in tissue fibrosis as well as in inflammatory conditions. The recent transcriptional profiling of what has been called “the pan-fibroblast cell lineage” in mouse and human tissues has identified novel transcriptional biomarker mRNAs encoding the secreted ECM proteins dermatopontin and collagen XV as well as the phosphatidylinositol-anchored membrane protein Pi16. Some of the genes identified in these fibroblasts scRNA-seq datasets will be useful for rigorous comparative characterizations of fibroblast-derived cell subpopulations. At the same time, it will be a challenge in the coming years to validate these transcriptional mRNA datasets at the protein-(expression) and at tissue-(distribution) levels and to find useful protein biomarker reagents that will facilitate fibroblast profiling at the cell level. In the current review we will focus on the role of the collagen-binding integrin α11β1 in CAFs, summarizing our own work as well as published datasets with information on α11 mRNA expression in selected tumors. Our experimental data suggest that α11β1 is more than just another biomarker and that it as a functional collagen receptor in the TME is playing a central role in regulating collagen assembly and matrix remodeling, which in turn impact tumor growth and metastasis.

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TGFβ Signaling Activated by Cancer-Associated Fibroblasts Determines the Histological Signature of Lung Adenocarcinoma

Cited by 37 publications

References 47 publications

The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer

The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Integrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?

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