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Tumor-microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma

ABSTRACT: To better understand the interaction between tumor cells and their microenvironment with regard to mechanisms of invasion, total RNA was isolated from the inner-tumor, tumor invasion front, adjacent lung and distant normal lung tissue from 18 patients with squamous cell lung carcinoma using punch-aided laser capture microdissection. Comprehensive mRNA expression profiles were obtained from microarray expreiments and statistical analyses revealed extensive changes in gene expression when comparing the inner tumor and tumor front with the normal lung and lung front. However, only a few genes were differentially expressed between the tumor front and the inner tumor. The identified genes indicate prostaglandin mediated inflammatory processes at the invasion front

ORGANISM(S): Homo sapiens

PROVIDER: GSE31446 | GEO | 2011/12/01

SECONDARY ACCESSION(S): PRJNA145815

REPOSITORIES: GEO

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Tumor-microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma

Project description:To better understand the interaction between tumor cells and their microenvironment with regard to mechanisms of invasion, total RNA was isolated from the inner-tumor, tumor invasion front, adjacent lung and distant normal lung tissue from 18 patients with squamous cell lung carcinoma using punch-aided laser capture microdissection. Comprehensive mRNA expression profiles were obtained from microarray expreiments and statistical analyses revealed extensive changes in gene expression when comparing the inner tumor and tumor front with the normal lung and lung front. However, only a few genes were differentially expressed between the tumor front and the inner tumor. The identified genes indicate prostaglandin mediated inflammatory processes at the invasion front Sample for microarray experiments were taken from the inner-tumor, tumor invasion front, adjacent lung and distant normal lung tissue from 18 patients with squamous cell lung carcinoma using punch-aided laser capture microdissection. Sample RNA and Universal Reference RNA (Stratagene, La Jolla, USA) were amplified and separately labeled with both Cy3 and Cy5. All samples were subjected to two-color hybridizations (sample against reference) with color-switch experiments yielding two technical replicates, respectively.

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Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion

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Downregulation of miR-218-5p promotes invasion of oral squamous cell carcinoma cells via activation of CD44-ROCK signaling

Project description:The invasion front of oral squamous cell carcinoma (OSCC) harbors the most aggressive cells of the tumor and is critical for cancer invasion and metastasis. MicroRNAs (miRNAs) play an important role in regulating OSCC invasion. In this study, we modeled the OSCC invasion front on a microfluidic chip and investigated differences in miRNA profiles between cells in the invasion front and those in the tumor mass by small RNA sequencing and bioinformatic analysis. We found that miR-218-5p was downregulated in invasion front cells; a luciferase reporter assay confirmed that cluster of differentiation (CD)44 was a direct target of miR-218-5p. Inhibiting miR-218-5p in invasion front cells activated CD44- Rho-associated protein kinase (ROCK) signaling and promoted cell invasion by inducing cytoskeletal reorganization. These findings indicate that miR-218-5p negatively regulates OSCC invasiveness by targeting the CD44–ROCK pathway and may be a useful therapeutic target for OSCC. Moreover, our method of modeling and isolating invasion front cells using a microfluidic chip is a time-saving alternative to in vivo models.

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Project description:We collected matched pairs of primary tumor (invasive front and intra-tumor region), metastatic region and adjacent normal tissue from head and neck squamous cell carcinoma patients at the Taipei Veterans General Hospital (TVGH) for RNA sequencing analysis.

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Liquid chromatography-mass spectrometry based tissue metabolic profiling reveals major metabolic pathway alterations and potential biomarkers of lung cancer

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Comparison of transcriptomic profiles in natural populations of rodents (house mouse and black rat) along invasion routes in Senegal

Project description:We compared gene expression proﬁles between anciently and recently established populations of two major invading species, the black rat Rattus rattus and the house mouse Mus musculus musculus, in Senegal. Transcriptome analyses revealed respectively 364 and 83 differentially expressed genes along the mouse and rat invasion routes. Among them, 10 and 15% were annotated with functions related to immunity. All immune-related genes detected along the mouse invasion route were over-expressed at the invasion front. Genes of the complement activation pathway were over-represented. Results were less straightforward when considering the black rat. No particular immune pathway was over-represented. In conclusion, we revealed changes in transcriptomic profiles along invasion routes. Patterns differed between invaders. They could potentially be driven by increased infection risks at invasion front for the house mouse and trade-offs between immune responses for the black rat. Our results provide a first step in identifying the immune ecoevolutionary processes potentially involved in invasion success.

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Drosha/Dicer/miR-7/TGF-β2 axis Sustained Acidic Microenvironment-induced Lung Metastasis

Project description:Extracellular pH (pHe) is lower in many tumors than in the corresponding normal tissue. Acidic tumor microenvironment has been shown to facilitate epithelial mesenchymal transition (EMT) and tumor metastasis, while the mechanisms underlying tumor acidic microenvironment-induced tumor cell metastasis remain undefined. Here, we aimed to investigate the tumor metastasis and the EMT by acidic microenvironment and to explore their mechanisms and clinical significance in lung cancer. Results showed that acidic pHe remarkably enhanced invasion ability of lung cells accompanying with increased mesenchymal and decreased epithelial markers. Moreover, acidic pHe triggered the inhibition of microRNA-7 (miR-7) expression and activation of TGF-β2/SMAD signaling. Mechanistic studies showed that TGF-β2 is a direct potential target gene of miR-7, and acidity-induced metastasis could be abolished by treatment with a TGFβRI inhibitor, anti-TGF-β2 antibody and miR-7 mimic, respectively. The clinical samples further revealed that miR-7 was decreased in lung tissues and antagonistically correlated with TGF-β2 expression, associating with overall survival and metastasis. In conclusion, our study indicated that acidic pHe showed enhanced invasive potential, and enhanced potential to develop experimental metastases by a novel mechanism involving tumor acidic microenvironment-induced regulation of miR-7/TGF-β2/SMAD axis. Our findings suggest that the possibility that pHe of the primary tumor may be an important prognostic parameter for lung cancer patients merit clinical investigation. Moreover, miR-7 may serve as prognostic molecular marker and a novel therapeutic target for lung cancer.

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