Unknown,Transcriptomics,Genomics,Proteomics

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Expression profiling of secreted and cell surface genes of 5 transformed cell lines and derivative xenograft tumors

ABSTRACT: Since the early stages of tumorigenesis involve adhesion, escape from immune surveillance, vascularization and angiogenesis, we devised a strategy to study the expression profiles of all publicly known and putative secreted and cell surface genes. We designed a custom oligonucleotide microarray containing probes for 3531 secreted and cell surface genes to study 5 diverse human transformed cell lines and their derivative xenograft tumors. The origins of these human cell lines were lung (A549), breast (MDA MB-231), colon (HCT-116), ovarian (SK-OV- 3) and prostate (PC3) carcinomas. Three different analyses were performed: (1) A PCA-based linear discriminant analysis identified a 54 gene profile characteristic of all tumors when pooled tumor data were analyzed, (2) Application of MANOVA (P Pcorr corr < .05) to pooled tumor data revealed a larger set of 149 differentially expressed genes. (3) After MANOVA was performed on data from individual tumors, a comparison of differential genes amongst all tumor types revealed 12 common differential genes. Seven of the 12 genes were identified by all three analytical methods. These included late angiogenic, morphogenic and extracellular matrix genes such as ANGPTL4, COL1A1, GP2, GPR57, LAMB3, PCDHB9 and PTGER3. The differential expression of ANGPTL4 and COL1A1 and other genes was confirmed by quantitative PCR. Overall, a comparison of the three analyses revealed an expression pattern indicative of late angiogenic processes. These results show that a xenograft model using multiple cell lines of diverse tissue origin can identify common tumorigenic cell surface or secreted molecules that may be important biomarker and therapeutic discoveries.

ORGANISM(S): Homo sapiens

SUBMITTER: Yan Lu

PROVIDER: E-GEOD-2179 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Webb2002 - Fas/FasL mediated tumor T-cell interaction This deterministic model of immunological surveillance involving tumour cell–T-lymphocyte interaction, cell surface expression of Fas/FasL, and their secreted soluble forms. This model is described in the article: Cells behaving badly: a theoretical model for the Fas/FasL system in tumour immunology. Webb SD, Sherratt JA, Fish RG. Math Biosci 2002 Sep-Oct; 179(2): 113-129 Abstract: One proposed mechanism of tumour escape from immune surveillance is tumour up-regulation of the cell surface ligand FasL, which can lead to apoptosis of Fas receptor (Fas) positive lymphocytes. Based upon this 'counterattack', we have developed a mathematical model involving tumour cell-lymphocyte interaction, cell surface expression of Fas/FasL, and their secreted soluble forms. The model predicts that (a) the production of soluble forms of Fas and FasL will lead to the down-regulation of the immune response; (b) matrix metalloproteinase (MMP) inactivation should lead to increased membrane FasL and result in a higher rate of Fas-mediated apoptosis for lymphocytes than for tumour cells. Recent studies on cancer patients lend support for these predictions. The clinical implications are two-fold. Firstly, the use of broad spectrum MMP inhibitors as anti-angiogenic agents may be compromised by their adverse effect on tumour FasL up-regulation. Also, Fas/FasL interactions may have an impact on the outcome of numerous ongoing immunotherapeutic trials since the final common pathway of all these approaches is the transduction of death signals within the tumour cell. This model is hosted on BioModels Database and identified by: BIOMD0000000661. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Expression profiling of secreted and cell surface genes of 5 transformed cell lines and derivative xenograft tumors

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