Tumor‐associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen

Qiu, Shi; Deng, Liangliang; Liao, Xinyang; Nie, Ling; Fang, Qi; Jin, Kun; Tu, Xiang; Zheng, Xiaonan; Li, Jiakun; Liu, Liangren; Liu, Zhenhua; Bao, Yige; Ai, Jianzhong; Lin, Tianhai; Yang, Lu; Wang, Qiang

doi:10.1111/cas.14078

Cited by 66 publications

(57 citation statements)

References 32 publications

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“…Among these types, COLI, COLIII, and COLV are mainly produced by fibroblasts, while COLIV is predominantly expressed by epithelial and endothelial cells. Notably, cancer cells and tumorassociated macrophages also produce collagen under some circumstances [20,21].…”

Section: Physiological and Physicochemical Properties Of Collagenmentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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Section: Physiological and Physicochemical Properties Of Collagenmentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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“…International Publisher was long applied for the treatment of BLCA [4,5]. The tumor microenvironment consists of immune cells, mesenchymal cells, endothelial cells, extracellular matrix (ECM) molecules, and inflammatory mediators [6].…”

Section: Ivyspringmentioning

confidence: 99%

Profiles of Immune Infiltration in Bladder Cancer and its Clinical Significance: an Integrative Genomic Analysis

Zhu

Liu

et al. 2020

Int. J. Med. Sci.

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Tumor-infiltrating immune cells are closely related to the prognosis of bladder cancer. Analysis of tumor infiltrating immune cells is usually based on immunohistochemical analysis. Since many immune cell marker proteins are not specific for different immune cells, which may induce misleading or incomplete. CIBERSORT is an algorithm to estimate specific cell types in a mixed cell population using gene expression data. In this study, the CIBERSORT algorithm was used to identify the immune cell infiltration signatures. The gene expression profiles, mutation data, and clinical data were collected from The Cancer Genome Atlas (TCGA) database. Unsupervised consensus clustering was used to acquire the immune cell infiltration subtypes of bladder cancer based on the fractions of 22 immune cell types. Four immune cell clusters with different immune infiltrate and mutation characteristics were identified. In addition, this stratification has a prognostic relevance, with cluster 2 having the best outcome, cluster 1 the worst. These clusters showed distinct mRNA expression patterns. The characteristic genes in subtype cluster 1 were mainly involved in cell division, those in subtype cluster 2 were mainly related in antigen processing and presentation, those in subtype cluster 3 were mainly involved in epidermal cell differentiation, and those in subtype cluster 4 were mainly related in the humoral immune response. These differences may affect the development of the bladder cancer, the sensitivity to treatment as well as the prognosis. Through further validation, this study may contribute to the development of personalized therapy and precision medical treatments.

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“…The PI3K/AKT/mTOR signaling pathway plays a significant role in tumor cell proliferation, growth and survival, in addition to modulating the tumor microenvironment and tumor-associated macrophages (TAMs) [41][42][43][44][45][46][47] . ECM and focal adhesion molecules, including PLXDC2, PDGFRB, FSTL1, TIMP2, FAP, SPARC, AEBP1, NOX4, and FBLN2 are known to regulate macrophage mobilization into tumor tissues 19,20,[48][49][50] , and are associated with TAM 51-53 . Therefore, it is possible that VGLL3 also modulates TAM via at least some of those genes.…”

Section: Discussionmentioning

confidence: 99%

VGLL3 is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in stomach adenocarcinoma

Zhang

Mao

et al. 2020

Sci Rep

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Due to its poor clinical outcome, there is an urgent need to identify novel prognostic markers for stomach adenocarcinoma (STAD). Here, we aimed to explore the relationship between VGLL3 expression and clinico-pathological features, dendritic cells, macrophages, and prognosis of STAD. VGLL3 expression levels were significantly associated with histological grade, T stage, and TNM stage. VGLL3 levels and patient's age were also independent prognostic factors of the clinical outcome of STAD. In addition, VGLL3 was associated with the abundance of macrophages and dendritic cells in tumor infiltrates, of which only VGLL3 and macrophage counts were the independent prognostic factors of immune cell infiltration in the TIMER Database. Extracellular matrix receptor interaction, focal adhesion, pathways in cancer, MAPK, JAK STAT, and WNT signaling pathways were enriched in VGLL3 high-expressing datasets as determined by Gene Set Enrichment Analysis (GSEA), while DNA replication, glyoxylate, and dicarboxylate metabolism, glutathione metabolism, homologous recombination, and glycosylphosphatidylinositol gpi banchor biosynthesis were enriched in VGLL3 low-expressing datasets. Thus, VGLL3 is a novel prognostic biomarker of both the clinical outcome and immune infiltration in STAD, and may therefore be a promising therapeutic target.Despite advances in treatment modalities, gastric cancer remains the most common cause of cancer-related deaths in Asia, and the second most common cause of death worldwide 1 . Around 90% to 95% of gastric cancer cases involve stomach adenocarcinomas (STAD) 2 . Although the survival of STAD patients has greatly improved in the past 20 years due to surgery, chemotherapy and targeted therapy, the prognosis is still unsatisfactory 3 . Poor differentiation, late diagnosis, lack of predictive markers, and ineffective therapeutic targets are key factors that drive STAD metastasis and recurrence 4 . Therefore, it is essential to explore the molecular mechanisms underlying STAD development and progression to identify novel prognostic biomarkers and potential therapeutic targets to treat gastric cancer.Transcription cofactor vestigial-like protein 3 (VGLL3) is a coactivator of mammalian toxicity equivalency factors (TEFs), and was associated with breast cancer, colon cancer, and lung cancer among other malignancies 5-9 . In our previous study, we found that VGLL3 at the protein level as determined by immunohistochemistry (IHC) was a novel prognostic biomarker for gastric cancer in the Chinese population 10 . However, its role at the mRNA level of STAD and immune microenvironment remains to be elucidated. To determine whether VGLL3 was involved in the progression of STAD, the Wilcox test and Kruskal test method were used to analyze the differences in VGLL3 expression in subgroups of clinic-pathological trait. Cox regression and log-rank test were used to evaluate significance of VGLL3 on disease prognosis.Recently, more and more evidence showed immune cell infiltration plays a vital role in predicting overall...

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Tumor‐associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen

Cited by 66 publications

References 32 publications

The role of collagen in cancer: from bench to bedside

The role of collagen in cancer: from bench to bedside

Profiles of Immune Infiltration in Bladder Cancer and its Clinical Significance: an Integrative Genomic Analysis

VGLL3 is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in stomach adenocarcinoma

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