Expression analysis of secreted and cell surface genes of five transformed human cell lines and derivative xenograft tumors.
BACKGROUND
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.


RESULTS
Three different analyses were performed: (1) A PCA-based linear discriminant analysis identified a 54 gene profile characteristic of all tumors, (2) Application of MANOVA (Pcorr < .05) to 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.


CONCLUSIONS
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.
Stull
Robert A
RA
PPD Discovery, 1505 O'Brien Street, Menlo Park, California 94025, USA. robert.stull@menlo.ppdi.com
Tavassoli
Roya
R
Kennedy
Scot
S
Osborn
Steve
S
Harte
Rachel
R
Lu
Yan
Y
Napier
Cheryl
C
Abo
Arie
A
Chin
Daniel J
DJ
D000704:Analysis of Variance; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D005821:Genetic Techniques; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D015999:Multivariate Analysis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D005819:Genetic Markers; D008565:Membrane Proteins; D012313:RNA