Identification of Cancer-Associated Fibroblast Subtype of Triple-Negative Breast Cancer

Wang, Maoli; Feng, Ruifa; Chen, Zihao; Shi, Wenjie; Li, Cheng; Liu, Huiquan; Wu, Kangning; Li, Dajin; Li, Xiqing

doi:10.1155/2022/6452636

Cited by 15 publications

(12 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the remodeling steps during tumor growth, the normal ECM collagens are substituted with a tumor-specific collagen profile [ 70 ]. Increased expression of different collagens was associated with tumor progression and a poor prognosis in various types of epithelial cancers including colorectal [ 71 ], esophagus [ 72 ], glioma [ 73 ], gastric [ 74 , 75 ], head and neck [ 76 ], lung [ 77 ], ovarian [ 78 ], pancreatic [ 79 ], renal [ 80 ], breast [ 81 , 82 ], and cervical cancer [ 83 ]. The profile of different collagen types expressed in various solid cancers is presented as a heatmap in Figure 2 .…”

Section: Collagen Family and Cancermentioning

confidence: 99%

Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer

Necula

Matei²,

Dragu³

et al. 2022

IJMS

View full text Add to dashboard Cite

Despite advances in cancer detection and therapy, it has been estimated that the incidence of cancers will increase, while the mortality rate will continue to remain high, a fact explained by the large number of patients diagnosed in advanced stages when therapy is often useless. Therefore, it is necessary to invest knowledge and resources in the development of new non-invasive biomarkers for the early detection of cancer and new therapeutic targets for better health management. In this review, we provided an overview on the collagen family as promising biomarkers and on how they may be exploited as therapeutic targets in cancer. The collagen family tridimensional structure, organization, and functions are very complex, being in a tight relationship with the extracellular matrix, tumor, and immune microenvironment. Moreover, accumulating evidence underlines the role of collagens in promoting tumor growth and creating a permissive tumor microenvironment for metastatic dissemination. Knowledge of the molecular basis of these interactions may help in cancer diagnosis and prognosis, in overcoming chemoresistance, and in providing new targets for cancer therapies.

show abstract

Section: Collagen Family and Cancermentioning

confidence: 99%

Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer

Necula

Matei²,

Dragu³

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…COL11A1 is a known marker of CAFs [40][41][42][43], but COL10A1 is a novel PDAC CAF marker. COL10A1 has been associated with CAFs in breast cancer [44]. Actually, one study found that a specific CAF subtype in breast cancer, associated with an immunosuppressive TME, was unique in its increased expression of specific collagens, including type VIII, X, and XI collagens [45].…”

Section: Discussionmentioning

confidence: 99%

The collagen landscape in cancer: profiling collagens in tumors and in circulation reveals novel markers of cancer‐associated fibroblast subtypes

Thorlacius‐Ussing,

Jensen,

Nissen

et al. 2023

The Journal of Pathology

View full text Add to dashboard Cite

Cancer‐associated fibroblasts (CAFs) deposit and remodel collagens in the tumor stroma, impacting cancer progression and efficacy of interventions. CAFs are the focus of new therapeutics with the aim of normalizing the tumor microenvironment. To do this, a better understanding of CAF heterogeneity and collagen composition in cancer is needed. In this study, we sought to profile the expression of collagens at multiple levels with the goal of identifying cancer biomarkers. We investigated the collagen expression pattern in various cell types and CAF subtypes in a publicly available single‐cell RNA sequencing (RNA‐seq) dataset of pancreatic ductal adenocarcinoma. Next, we investigated the collagen expression profile in tumor samples across cancer types from The Cancer Genome Atlas (TCGA) database and evaluated if specific patterns of collagen expression were associated with prognosis. Finally, we profiled circulating collagen peptides using a panel of immunoassays to measure collagen fragments in the serum of cancer patients. We found that pancreatic stellate cells and fibroblasts were the primary producers of collagens in the pancreas. COL1A1, COL3A1, COL5A1, COL6A1 were expressed in all CAF subtypes, whereas COL8A1, COL10A1, COL11A1, COL12A1 were specific to myofibroblast CAFs (myCAF) and COL14A1 specific to inflammatory CAFs (iCAF). In TCGA database, myCAF collagens COL10A1 and COL11A1 were elevated across solid tumor types, and multiple associations between high expression and worse survival were found. Finally, circulating collagen biomarkers were elevated in the serum of patients with cancer relative to healthy controls with COL11A1 (myCAF) having the best diagnostic accuracy of the markers measured. In conclusion, CAFs express a noncanonical collagen profile with specific collagen subtypes associated with iCAFs and myCAFs in PDAC. These collagens are deregulated at the cellular, tumor, and systemic levels across different solid tumors and associate with survival. These findings could lead to new discoveries such as novel biomarkers and therapeutic targets. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

show abstract

“…Our 3D TNBC monoculture model may not fully reflect physiological conditions, thus we aimed to investigate the anti-tumor potential of ( 1 ) by mimicking the TNBC TME by inclusion of tumor-specific stromal cells and ECM-matrix components [ 107 ]. Spheroids were grown with additional type I collagen, the main component in the stroma of TNBC patients [ 108 ], mainly secreted by CAFs [ 43 ] and elevated in breast cancer [ 109 ].…”

Section: Discussionmentioning

confidence: 99%

Phenanthroindolizidine Alkaloids Isolated from Tylophora ovata as Potent Inhibitors of Inflammation, Spheroid Growth, and Invasion of Triple-Negative Breast Cancer

Reimche

Ariantari

et al. 2022

IJMS

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC), representing the most aggressive form of breast cancer with currently no targeted therapy available, is characterized by an inflammatory and hypoxic tumor microenvironment. To date, a broad spectrum of anti-tumor activities has been reported for phenanthroindolizidine alkaloids (PAs), however, their mode of action in TNBC remains elusive. Thus, we investigated six naturally occurring PAs extracted from the plant Tylophora ovata: O-methyltylophorinidine (1) and its five derivatives tylophorinidine (2), tylophoridicine E (3), 2-demethoxytylophorine (4), tylophoridicine D (5), and anhydrodehydrotylophorinidine (6). In comparison to natural (1) and for more-in depth studies, we also utilized a sample of synthetic O-methyltylophorinidine (1s). Our results indicate a remarkably effective blockade of nuclear factor kappa B (NFκB) within 2 h for compounds (1) and (1s) (IC50 = 17.1 ± 2.0 nM and 3.3 ± 0.2 nM) that is different from its effect on cell viability within 24 h (IC50 = 13.6 ± 0.4 nM and 4.2 ± 1 nM). Furthermore, NFκB inhibition data for the additional five analogues indicate a structure–activity relationship (SAR). Mechanistically, NFκB is significantly blocked through the stabilization of its inhibitor protein kappa B alpha (IκBα) under normoxic as well as hypoxic conditions. To better mimic the TNBC microenvironment in vitro, we established a 3D co-culture by combining the human TNBC cell line MDA-MB-231 with primary murine cancer-associated fibroblasts (CAF) and type I collagen. Compound (1) demonstrates superiority against the therapeutic gold standard paclitaxel by diminishing spheroid growth by 40% at 100 nM. The anti-proliferative effect of (1s) is distinct from paclitaxel in that it arrests the cell cycle at the G0/G1 state, thereby mediating a time-dependent delay in cell cycle progression. Furthermore, (1s) inhibited invasion of TNBC monoculture spheroids into a matrigel®-based environment at 10 nM. In conclusion, PAs serve as promising agents with presumably multiple target sites to combat inflammatory and hypoxia-driven cancer, such as TNBC, with a different mode of action than the currently applied chemotherapeutic drugs.

show abstract

Identification of Cancer-Associated Fibroblast Subtype of Triple-Negative Breast Cancer

Cited by 15 publications

References 56 publications

Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer

Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer

The collagen landscape in cancer: profiling collagens in tumors and in circulation reveals novel markers of cancer‐associated fibroblast subtypes

Phenanthroindolizidine Alkaloids Isolated from Tylophora ovata as Potent Inhibitors of Inflammation, Spheroid Growth, and Invasion of Triple-Negative Breast Cancer

Contact Info

Product

Resources

About