Unmasking carcinoma-associated fibroblasts: Key transformation player within the tumor microenvironment

Meng, Qingguo; Luo, Xin; Chen, Jiaxin; Wang, Di; Chen, Engeng; Zhang, Wei; Zhang, Guolin; Zhou, Wei; Xu, Jianbin; Song, Zhangfa

doi:10.1016/j.bbcan.2020.188443

Cited by 14 publications

(10 citation statements)

References 231 publications

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“…2) [120][121][122]. Of note, CAFs exert both protumorigenic and antitumorigenic effects during disparate stages of oncogenic advancement in an organ or contextspecific manner, which brings challenges to the area of CAFs-targeted therapy for cancer treatment [123,124].…”

Section: Cancer-associated Fibroblastsmentioning

confidence: 99%

Targeting the tumor stroma for cancer therapy

et al. 2022

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Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part of the tumor microenvironment, the tumor stroma is highly dynamic, heterogeneous and commonly tumor-type specific, and it mainly includes noncellular compositions such as the extracellular matrix and the unique cancer-associated vascular system as well as a wide variety of cellular components including activated cancer-associated fibroblasts, mesenchymal stromal cells, pericytes. All these elements operate with each other in a coordinated fashion and collectively promote cancer initiation, progression, metastasis and therapeutic resistance. Over the past few decades, numerous studies have been conducted to study the interaction and crosstalk between stromal components and neoplastic cells. Meanwhile, we have also witnessed an exponential increase in the investigation and recognition of the critical roles of tumor stroma in solid tumors. A series of clinical trials targeting the tumor stroma have been launched continually. In this review, we introduce and discuss current advances in the understanding of various stromal elements and their roles in cancers. We also elaborate on potential novel approaches for tumor-stroma-based therapeutic targeting, with the aim to promote the leap from bench to bedside.

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Section: Cancer-associated Fibroblastsmentioning

confidence: 99%

Targeting the tumor stroma for cancer therapy

et al. 2022

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“… 1 , 2 Similar to normal lymph nodes, TLSs provide a microenvironment for the recruitment of T cells, activation of B cells, and production of antibodies. 3 , 4 , 5 TLSs were initially found to correlate with favorable clinical outcomes in non‐small cell lung cancer (NSCLC), 6 and in other similar malignancies, such as gastric, breast, and colorectal cancers. 7 , 8 , 9 , 10 TLSs have been proven to improve antitumor responses and predict the efficacy of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Tertiary lymphoid structures (TLSs) are ectopic lymphoid formations with highly ordered T and B lymphocyte colonies found in nonlymphoid tissues 1,2 . Similar to normal lymph nodes, TLSs provide a microenvironment for the recruitment of T cells, activation of B cells, and production of antibodies 3–5 . TLSs were initially found to correlate with favorable clinical outcomes in non‐small cell lung cancer (NSCLC), 6 and in other similar malignancies, such as gastric, breast, and colorectal cancers 7–10 .…”

Section: Introductionmentioning

confidence: 99%

Tertiary lymphoid structures in lung adenocarcinoma: characteristics and related factors

et al. 2022

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Objective Tertiary lymphoid structures (TLSs) are found in a variety of malignancies and affect the growth of tumors, but few studies have addressed their role in lung adenocarcinoma (LAC). We aimed to evaluate clinical features associated with TLSs in patients with LAC. Methods and Materials A collection of resected pulmonary nodules in patients with LAC was retrospectively analyzed. TLSs were quantified by their number per square millimeter tumor area (density) and by the degree of lymphocyte aggregation (maturity) in each case. The correlation between TLS density and maturity and clinical features was calculated. Results A total of 243 patients were selected, of whom 219 exhibited TLSs. The occurrence of TLSs was correlated with computed tomography (CT) features as follows: pure ground‐glass nodules (pGGNs) (n = 43) was associated with a lower occurrence rate than part‐solid nodules (PSNs) (n = 112) and solid nodules (SNs) were (n = 88) (p = 0.037). TLS density was correlated with age and CT features. Poisson regression showed higher TLS density in PSNs and SNs than in pGGNs (incidence rate ratio [IRR]: 3.137; 95% confidence interval [CI]: 1.35–7.27; p = 0.008 and IRR: 2.44; 95% CI: 1.02–5.85; p = 0.046, respectively). In addition, TLS density was higher in patients aged under 60 years than in those aged over 60 years (IRR: 0.605; 95% CI: 0.4–0.92; p = 0.018). The maturity of TLSs was higher in patients with higher tumor stages (p = 0.026). Conclusions We demonstrated distinct profiles of TLSs in early LAC and their correlations with CT features, age, and tumor stages, which could help understand tumor progression and management.

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“…In this study, we confirmed the canonical Wnt/β‐catenin signalling pathway was overactivated in CD133 + CRC cells, and firstly documented that the expression of LRP5 was upregulated in CD133 + CRC cells. Interestingly, the analyses on CRC‐based GEO data set also showed it was obviously increased in CD133 + CRC cells as compared to that in carcinoma‐associated fibroblasts, a heterogeneous cell population arised from tumour‐infiltrating mesenchymal stem cells or resting fibroblasts and provide a tumour‐promoting microenvironment for tumour progression and metastasis 54 . An obvious positive correlation was also found between the mRNA levels of LRP5 and PROM1 (CD133) in CRC tissues.…”

Section: Discussionmentioning

confidence: 91%

LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer

Nie

Liu

et al. 2022

J Cellular Molecular Medi

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The overactivation of canonical Wnt/β‐catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low‐density lipoprotein receptor‐related protein 5 (LRP5) has been identified as an indispensable co‐receptor with frizzled family members for the canonical Wnt/β‐catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs‐like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/β‐catenin and IL‐6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs‐like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross‐talk between canonical Wnt/β‐catenin signalling pathway, IL‐6/STAT3 signalling pathway and CD133‐related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.

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Unmasking carcinoma-associated fibroblasts: Key transformation player within the tumor microenvironment

Cited by 14 publications

References 231 publications

Targeting the tumor stroma for cancer therapy

Targeting the tumor stroma for cancer therapy

Tertiary lymphoid structures in lung adenocarcinoma: characteristics and related factors

LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer

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