Research article

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

Robert A Stull¹ , Roya Tavassoli¹ , Scot Kennedy¹ , Steve Osborn¹ , Rachel Harte¹ , Yan Lu¹ , Cheryl Napier² , Arie Abo¹ and Daniel J Chin¹

¹  PPD Discovery, 1505 O'Brien Street, Menlo Park, California 94025, USA

²  Piedmont Research Center, Morrisville, North Carolina 27560, USA

author email corresponding author email

BMC Genomics 2005, 6:55doi:10.1186/1471-2164-6-55

Published:	18 April 2005

Abstract

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.

Conclusion

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.