A CAF-Fueled TIMP-1/CD63/ITGB1/STAT3 Feedback Loop Promotes Migration and Growth of Breast Cancer Cells

Dittmer, Angela; Dittmer, Jürgen

doi:10.3390/cancers14204983

Cited by 9 publications

(7 citation statements)

References 65 publications

(114 reference statements)

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“…As for the STAT3 signaling pathway, it has been shown that CAF-secreted TIMP-1 activated the STAT3 pathway in BC cells, promoting proliferation and migration, and CAF-derived IL-6 can increase extracellular TIMP-1 abundance, suggesting that inhibition of TIMP-1/CD63/integrin β1/STAT3 loop may be a promising therapeutic modality. In addition, CAF-derived IL-6 can directly activate the STAT3 pathway, promoting the growth and radioresistance of BC cells [ 265 , 266 ]. The primary representative inhibitors can be divided into peptides, small molecules, and oligonucleotides.…”

Section: Background Knowledge Of Cafsmentioning

confidence: 99%

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Zhang,

Yue,

Chen

et al. 2023

Mol Cancer

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Despite centuries since the discovery and study of cancer, cancer is still a lethal and intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as a pivotal component of the tumor microenvironment. The versatility and sophisticated mechanisms of CAFs in facilitating cancer progression have been elucidated extensively, including promoting cancer angiogenesis and metastasis, inducing drug resistance, reshaping the extracellular matrix, and developing an immunosuppressive microenvironment. Owing to their robust tumor-promoting function, CAFs are considered a promising target for oncotherapy. However, CAFs are a highly heterogeneous group of cells. Some subpopulations exert an inhibitory role in tumor growth, which implies that CAF-targeting approaches must be more precise and individualized. This review comprehensively summarize the origin, phenotypical, and functional heterogeneity of CAFs. More importantly, we underscore advances in strategies and clinical trials to target CAF in various cancers, and we also summarize progressions of CAF in cancer immunotherapy.

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Section: Background Knowledge Of Cafsmentioning

confidence: 99%

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Zhang,

Yue,

Chen

et al. 2023

Mol Cancer

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“…TIMPS have been implicated in cancer progression and metastasis. For instance, CAF-secreted TIMP-1 initiates a STAT3 feedback loop that has been shown to play an integral part in breast cancer growth and migration [ 47 ].…”

Section: Cafs Modulate the Ecm Compositionmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Master Tumor Microenvironment Modifiers

Wright

Kriet

et al. 2023

Cancers

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Cancer cells rely on the tumor microenvironment (TME), a composite of non-malignant cells, and extracellular matrix (ECM), for survival, growth, and metastasis. The ECM contributes to the biomechanical properties of the surrounding tissue, in addition to providing signals for tissue development. Cancer-associated fibroblasts (CAFs) are stromal cells in the TME that are integral to cancer progression. Subtypes of CAFs across a variety of cancers have been revealed, and each play a different role in cancer progression or suppression. CAFs secrete signaling molecules and remodel the surrounding ECM by depositing its constituents as well as degrading enzymes. In cancer, a remodeled ECM can lead to tumor-promoting effects. Not only does the remodeled ECM promote growth and allow for easier metastasis, but it can also modulate the immune system. A better understanding of how CAFs remodel the ECM will likely yield novel therapeutic targets. In this review, we summarize the key factors secreted by CAFs that facilitate tumor progression, ECM remodeling, and immune suppression.

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“…This study further showed that blocking TIMP-1 activity using neutralizing antibody inhibits TNBC cell growth in vivo. CAF-derived TIMP-1 was involved in the migration and growth of breast cancer cells though TIMP-1/CD63/ITGB1/STAT3 feedback loop (115). Regarding the prognostic value and role of TIMP-2 and -3 in breast cancer, conflicting results have been reported.…”

Section: The Roles Of Tissue Inhibitors Of Mmps In Breast Cancermentioning

confidence: 99%

Matrix metalloproteinases as therapeutic targets in breast cancer

Kwon

2023

Front. Oncol.

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Matrix metalloproteinases (MMPs) are the most prominent proteinases involved in tumorigenesis. They were initially recognized to promote tumor progression by remodeling the extracellular matrix through their proteolytic activity. However, accumulating evidence has revealed that some MMPs have protective roles in cancer progression, and the same MMP can exert opposing roles depending on the cell type in which it is expressed or the stage of cancer. Moreover, studies have shown that MMPs are involved in cancer progression through their roles in other biological processes such as cell signaling and immune regulation, independent of their catalytic activity. Despite the prognostic significance of tumoral or stromal expression of MMPs in breast cancer, their roles and molecular mechanisms in breast cancer progression remain unclear. As the failures of early clinical trials with broad-spectrum MMP inhibitors were mainly due to a lack of drug specificity, substantial efforts have been made to develop highly selective MMP inhibitors. Some recently developed MMP inhibitory monoclonal antibodies demonstrated promising anti-tumor effects in preclinical models of breast cancer. Importantly, anti-tumor effects of these antibodies were associated with the modulation of tumor immune microenvironment, suggesting that the use of MMP inhibitors in combination with immunotherapy can improve the efficacy of immunotherapy in HER2-positive or triple-negative breast cancer. In this review, the current understanding of the roles of tumoral or stromal MMPs in breast cancer is summarized, and recent advances in the development of highly selective MMP inhibitors are discussed.

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A CAF-Fueled TIMP-1/CD63/ITGB1/STAT3 Feedback Loop Promotes Migration and Growth of Breast Cancer Cells

Cited by 9 publications

References 65 publications

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Cancer-Associated Fibroblasts: Master Tumor Microenvironment Modifiers

Matrix metalloproteinases as therapeutic targets in breast cancer

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