Tumor Microenvironment and Hemorheological Abnormalities

Baronzio, Gianfranco; Freitas, Isabel; Kwaan, Hau C.

doi:10.1055/s-2003-44557

Cited by 26 publications

(9 citation statements)

References 50 publications

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“…Tissue interstitial fluid (TIF) is another sample that has gained increasing attention as a substrate from which candidate protein biomarker discovery can be made. The production of TIF results from build-up of fluid derived from cell secretions due to a lack of a vascular and lymphatic system within the tumor [5]. Because this fluid is directly associated with the tumor, it may be a rich source of tumor-specific biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of non-small cell lung cancer tissue interstitial fluids

Wang

Zhang

et al. 2013

World J Surg Onc

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BackgroundNon-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers, and reliable biomarkers are desirable. The present investigation assesses our ability to identify tumor relevant proteins from NSCLC tissue interstitial fluid (TIF).MethodsPaired TIF was collected from three NSCLC patients at the time of surgery, and resolved by two-dimensional gel electrophoresis and in-gel digestion for proteomic analysis. Differentially expressed spots were extracted from the two-dimensional gel and characterized by high-performance liquid chromatography-tandem mass spectrometry. Then, ELISA was used to verify the expression of peroxiredoxin 1 (PRDX1) in TIF of patients with NSCLC and benign lung disease. Finally, the relationship between expression of PRDX1 and clinicopathological features was determined.ResultsComparative proteomic analysis showed 24 protein spots were differentially expressed with significant changes, including 11 upregulated proteins and 13 downregulated proteins. Of these, PRDX1 was selected for validation in TIF by Western blot and expression of PRDX1 was confirmed to be upregulated in tumor TIF. It was also demonstrated that PRDX1 was significantly elevated in 40 NSCLC patients with a mean level of 36.0 ng/mL compared to 6.26 ng/mL from 20 patients with benign lung disease. A significant correlation was found between the high level of PRDX1 expression and lymph node metastasis and tumor differentiation.ConclusionsPRDX1 might be correlated with lymph node metastasis and differentiation, and its elevated expression in TIF may be an adverse biomarker for patients with NSCLC. PRDX1 may be attributed to the malignant transformation of NSCLC, and attention should be paid to a possible target for therapy.

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Section: Introductionmentioning

confidence: 99%

Proteomic analysis of non-small cell lung cancer tissue interstitial fluids

Wang

Zhang

et al. 2013

World J Surg Onc

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“…Interestingly, the receptor for CSF2, CSF2RA, is also significantly overexpressed in THP-1. Clearly, future experiments will be needed to address other roles of CSF2 in the tumor-stroma crosstalk such as suggested contributions in the recruitment of monocytes, macrophages and neutrophils into the tumor vicinity [ 89 , 90 , 91 ]. Our organotypic 3D models consisting of human tumor cells, stromal FBs and immune cells (or their respective precursors) represent valuable models which will allow to appropriately characterize the mechanisms of crosstalk in those triple cultures.…”

Section: Resultsmentioning

confidence: 99%

High EMT Signature Score of Invasive Non-Small Cell Lung Cancer (NSCLC) Cells Correlates with NFκB Driven Colony-Stimulating Factor 2 (CSF2/GM-CSF) Secretion by Neighboring Stromal Fibroblasts

et al. 2015

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We established co-cultures of invasive or non-invasive NSCLC cell lines and various types of fibroblasts (FBs) to more precisely characterize the molecular mechanism of tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown to contribute to the onset of the invasive phenotype of Calu-1 with HGF being secreted by FBs. Differential expression analysis of the respective mono- and co-cultures revealed an upregulation of NFκB-related genes exclusively in co-cultures with Calu-1. Cytokine Array- and ELISA-based characterization of the “cytokine fingerprints” identified CSF2 (GM-CSF), CXCL1, CXCL6, VEGF, IL6, RANTES and IL8 as being specifically upregulated in various co-cultures. Whilst CXCL6 exhibited a strictly FB-type-specific induction profile regardless of the invasiveness of the tumor cell line, CSF2 was only induced in co-cultures of invasive cell lines regardless of the partnered FB type. These cultures revealed a clear link between the induction of CSF2 and the EMT signature of the cancer cell line. The canonical NFκB signaling in FBs, but not in tumor cells, was shown to be responsible for the induced and constitutive CSF2 expression. In addition to CSF2, cytokine IL6, IL8 and IL1B, and chemokine CXCL1 and CXCL6 transcripts were also shown to be increased in co-cultured FBs. In contrast, their induction was not strictly dependent on the invasiveness of the co-cultured tumor cell. In a multi-reporter assay, additional signaling pathways (AP-1, HIF1-α, KLF4, SP-1 and ELK-1) were found to be induced in FBs co-cultured with Calu-1. Most importantly, no difference was observed in the level of inducibility of these six signaling pathways with regard to the type of FBs used. Finally, upon tumor fibroblast interaction the massive induction of chemokines such as CXCL1 and CXCL6 in FBs might be responsible for increased recruitment of a monocytic cell line (THP-1) in a transwell assay.

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“…Some of these differences are reversible, whereas others persist when the fibroblasts are removed from the vicinity of the carcinoma cells. Their gene expression differences are due to epigenetic and genetic alterations [13,14] and relate to the stage of their differentiation [15]. The evidence above shows that CAFs, like tumor cells, are heterogenous, not only between different but also within the same type of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Macrophage density in the tumor generally negatively correlates with relapse-free and overall survival but localization also seems to be important. The association between TAM (tumor associated macrophage)-density and survival of cancer patients depends on the intratumoral or peritumoral macrophages counted [15]. TAMs promote the metastatic capacity of cancer cells in stromal or perivascular areas, while around the necrosis, in a hypoxic state, they stimulate angiogenesis [64].…”

Section: Introductionmentioning

confidence: 99%

The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance

et al. 2014

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Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome.

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Tumor Microenvironment and Hemorheological Abnormalities

Cited by 26 publications

References 50 publications

Proteomic analysis of non-small cell lung cancer tissue interstitial fluids

Proteomic analysis of non-small cell lung cancer tissue interstitial fluids

High EMT Signature Score of Invasive Non-Small Cell Lung Cancer (NSCLC) Cells Correlates with NFκB Driven Colony-Stimulating Factor 2 (CSF2/GM-CSF) Secretion by Neighboring Stromal Fibroblasts

The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance

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