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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.

2011-12-01 | E-GEOD-31446 | biostudies-arrayexpress

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.

2018-05-21 | GSE107243 | GEO

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

Project description:Cancer-associated fibroblasts (CAFs) promote tumor progression through several mechanisms. MicroRNAs (miRNAs) play a key role in CAFs tumor-promoting properties, however, their role in CAFs from different topological areas in lung cancer progression remains unclear. This study aimed to characterize the miRNA expression profile of fibroblasts isolated from matched tumor front (F-CAFs), inner tumor (In-CAFs), and normal adjacent tissue (NFs) in lung adenocarcinoma, using microarray analysis and RT-qPCR. Proliferation and invasion assays of A549 lung cancer cells were performed in the presence of conditioned medium from F-CAFs, In-CAFs and NFs. Pathway enrichment analysis and miRNA-target networks were performed to identify tumorigenesis-related miRNAs. Both F-CAFs and In-CAFs enhanced the proliferation and invasion of A549 cells compared to NFs; however, F-CAFs showed a significantly stronger effect than In-CAFs. qPCR demonstrated three downregulated miRNAs in F-CAFs versus NFs (miR-145-3p, miR-299-3 p, miR-505-3p) and two in F-CAFs versus In-CAFs (miR-410-3p, miR-485-5p). Deregulated miRNAs showed significant association to “pathways in cancer”, “Wnt signaling pathway”, and “TGF-beta signaling pathway”, targeting tumor-promoting growth factors as IGF1 and VEGFA. Our findings suggest that deregulated miRNAs in F-CAFs, which showed the strongest effect on the invasive and proliferative capacity of A546 cancer cells, present potential predictive association with tumor-promoting properties.

2018-04-28 | GSE113805 | GEO

Expression profiling of stage IIA/MSS colon cancers from whole tumor and invasion front sampling

Project description:The goal was to identify gene expression signatures predictive of early relapse among stage IIA/MSS colon cancer patients. A secondary question addressed was whether the invasion front profiles could generate a competitive signature. 39 whole tumor and 35 matched invasion front profiles were generated (4 samples failed) and grouped into \\"early relapse\\" (relapse within 5 years) and \\"no relapse\\" (no relapse for at least 6 years) categories.

2024-03-25 | E-MTAB-13695 | biostudies-arrayexpress

Project description:Gene flow on an invasion front

| PRJNA476867 | ENA

Snail1 controls fibroblast action on tumor cell invasion and metastasis [HT29]

Project description:Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here that Snail1 plays also a key role in tumor associated fibroblasts since is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-b; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that tumor cells co-transplanted with Snail1 depleted fibroblasts show lower invasion than those xenografted with control fibroblasts. Finally Snail1 depletion in mice prevents the formation of breast tumors and decreased their invasion. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to its effect in EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial cells.

2016-12-22 | GSE74056 | GEO

Snail1 controls fibroblast action on tumor cell invasion and metastasis [MSC]

2016-12-22 | GSE74057 | GEO

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.

2021-04-09 | GSE112890 | GEO

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

Project description: Not available

| S-ECPF-GEOD-31446 | biostudies-other

Expression data from 36 KRAS-mutant lung adenocarcinomas from the BATTLE-2 clinical trial.

Project description:In this dataset, we include expression data from 36 KRAS-mutant lung adenocarcinomas from Stage 1 of the BATTLE-2 trial, reflecting patients whose disease has relapsed or progresses following at least one front-line metastatic chemotherapy regimen. Tumor biopsy was performed following informed consent and prior to randomisation to one of the four possible treatment arms.

2015-10-01 | GSE61913 | GEO

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