Cancer and the tumor microenvironment: a review of an essential relationship

Mbeunkui, Flaubert; Johann, Donald J.

doi:10.1007/s00280-008-0881-9

Cited by 417 publications

(326 citation statements)

References 95 publications

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“…Efforts to address this issue led to the sequence alignment between tTG and Human factor XIIIA, a hetero-tetrameric transglutaminase-family member implicated in blood coagulation (46). The X-ray crystal structure of the human recombinant, dimeric fXIIIA2 was determined in 1994 (47), and sequence homology between XIIIA and tTG predicted that tTG probably folded into four sequential domains: an N-terminal -sandwich domain, the central catalytic core domain, and two -barrel domains at the C-terminal end of this protein (48). This result was confirmed by the first tTG structure that was solved in 2002 at 2.8 Å resolution, which…”

Section: A Comparison Between the Active And Inactive Conformation Ofmentioning

confidence: 99%

Tissue Transglutaminase and its Role in Human Cancer Progression

Cerione

Antonyak

2011

Advances in Enzymology - And Related Areas of Molecular Biology

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Tissue transglutaminase (tTG) is a protein-crosslinking enzyme whose expression is up-regulated in several human cancers. Here I show that tTG is a key participant in a novel EGFR/Src-signaling pathway and a potential target for inhibiting EGFR-promoted tumor progression. Specifically, EGF up-regulates tTG expression in human breast cancer cells, and knock-downs of tTG expression or the treatment of breast cancer cells with a tTG-specific inhibitor, blocks EGF-stimulated anchorageindependent growth. The combined actions of Ras and Cdc42, lead to the activation of PI 3-kinase and NFκB, mediating the EGF-dependent up-regulation of tTG in breast cancer cells. Moreover, overexpression of wild-type tTG in these cancer cells, but not its enzymatically-defective counterpart, fully mimics the actions of EGF. Surprisingly, the tTG-promoted growth of breast cancer cells is dependent on its ability to activate BIOGRAPHICAL SKETCHBo Li was born and raised in Qingdao, a beautiful city on the eastern coast of China. During his childhood, his whole family lived in the vicinity of Qingdao Ocean University, due to the fact that his father worked there as a marine biologist.Occasionally Bo was brought to the laboratory where his father was doing research, and he was deeply attracted by the various biology and chemistry experiments that were performed there. Holding this strong curiosity towards science, he finished his secondary school in Qingdao and went to Peking University to pursue further education. He chose Chemistry as his major and became interested in working on biological questions using his Chemistry knowledge and background. This was the primary reason that he decided to join Dr. Luhua Lai's group, whose major research interests were the predication and modeling of protein structures, as well as the computed-aided drug design. Bo worked in her lab for three years as an undergraduate student and research assistant, on the project focusing on designing small-molecule inhibitors against Human Leukocyte Antigen-Death Receptor 4, an immuno-receptor linked to the progression of rheumatoid arthritis. After graduation from Peking University, he was fortunate enough to be accepted by the Chemistry department of Cornell University, and then became a Ph.D. student in Dr. Richard Cerione's group.There he switched his research focus from theoretical drug design to cell biology, doing research related to the function of a particular enzyme called tissue transglutaminase，and also one type of unconventional secretory structures called microvesicles, which carry tissue transglutaminase as their cargo. Although the life as iii a bio-researcher was not easy, he did enjoy every minute spent in the Cerione group, due to the consistent excitation of working on cutting-edge questions, as well as the family-like atmosphere always existed in this crowd. After graduation, he plans to start his postdoctoral training in the laboratory of Dr. M. Celeste Simon at the University of Pennsylvania, where he will study the mechanism of hypoxia, which ...

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Section: A Comparison Between the Active And Inactive Conformation Ofmentioning

confidence: 99%

Tissue Transglutaminase and its Role in Human Cancer Progression

Cerione

Antonyak

2011

Advances in Enzymology - And Related Areas of Molecular Biology

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“…Both inflammatory and stromal cells are important for tumor progression. 2,3 In cervical carcinoma there is a high amount of inflammatory infiltrate, and we have recently shown a correlation between a high number of intraepithelial regulatory T cells (Treg) and poor survival of cervical carcinoma patients. 4 Stromal cells produce growth factors and extracellular matrix (ECM) components and provide an adequate environment for angiogenesis.…”

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confidence: 99%

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

et al. 2010

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Cervical carcinoma is the second most frequent cancer type in women worldwide. Both inflammatory cells and stromal cells are important for tumor progression. Stromal cells produce growth factors and extracellular matrix and provide an adequate environment for angiogenesis. Versican, a member of the extracellular matrix, has been shown to have a role in tumor progression. The aim of this study was to investigate versican expression, and its association with tumor-infiltrating inflammatory cell subsets and with clinicopathological parameters in human cervical cancers. We have studied the expression of versican in 149 cervical cancers using immunohistochemistry and mRNA in situ hybridization. Versican was predominantly expressed in the stroma (myofibroblasts). Using quantitative real-time-PCR, V0 was found to be the most prominent isoform. High stromal versican expression was significantly associated with a low number of tumor-infiltrating T cells (P ¼ 0.018) and particularly a low number of CD8-positive T cells (cytotoxic T cells; P ¼ 0.002). Stromal versican expression was significantly higher in patients with an infiltration depth 414 mm (P ¼ 0.004) and in patients with parametrial invasion (P ¼ 0.044). Stromal versican expression was not associated with survival. Our results suggest that versican expression in the stromal compartment of cervical cancers results in reduced numbers of intraepithelial CD8-positive T cells and enhanced local invasion.

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“…However, several studies have indicated that tumor pathogenesis and progression are closely associated with the tumor microenvironment, as well as tumor cells themselves (13). Recent studies have suggested that a systemic inflammatory state is associated with the malignant biological behavior of the tumor (14,15).…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood neutrophil count as a prognostic factor for patients with hepatocellular carcinoma treated with sorafenib

Yuan

Liang

et al. 2017

Molecular and Clinical Oncology

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Abstract. Sorafenib is currently the only efficient molecular targeted therapy for hepatocellular carcinoma (HCC), although its effect is relatively moderate and variable between individuals. The present study aimed to evaluate the significance of peripheral blood neutrophils in the prognosis of HCC patients treated with sorafenib. A total of 464 patients with HCC were treated with sorafenib at Zhongshan Hospital (Shanghai, China) between January 1st, 2008 and December 31st, 2012, among which 120 patients were enrolled in the study. The optimal cutoff point for low vs. high neutrophil count (3.65x10 9 ) was obtained from a receiver operating characteristic curve. Overall survival (OS) was compared between the patients with low and high peripheral neutrophil counts. Univariate and multivariate analyses were used to explore the prognostic factors associated with OS in the patients treated with sorafenib. A nomogram model was also performed to predict the OS times of these patients. The median OS time was 9.0 months (95% confidence interval, 5.9-12.1 months) in the whole group of patients, with 1-, 2-and 3-year OS rates of 36, 24 and 16%, respectively. Using a cutoff level of 3.65x10 9 neutrophils/l, the median OS time was longer in the group of patients with a low peripheral neutrophil count than in those with a high peripheral neutrophil count (11.5 vs. 5.0 months, respectively; P<0.001). The multivariate analysis showed that peripheral neutrophil count, α-fetoprotein level and tumor size were independent prognostic factors for OS. In addition, using the nomogram model for the prediction of OS, the Harrell's c-index was 0.79. Therefore, it was concluded that a lower peripheral blood neutrophil count was associated with a better prognosis following treatment with sorafenib therapy.

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Cancer and the tumor microenvironment: a review of an essential relationship

Cited by 417 publications

References 95 publications

Tissue Transglutaminase and its Role in Human Cancer Progression

Tissue Transglutaminase and its Role in Human Cancer Progression

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

Peripheral blood neutrophil count as a prognostic factor for patients with hepatocellular carcinoma treated with sorafenib

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