Recent advances in gene expression profiling have led to the development of comprehensive databases which can be queried in various manners. In the present report, we have taken a list of genes previously associated with angiogenesis, either in in vivo or in in vitro models, and queried a commercial database established by GeneLogic® to determine the relative expression of these candidate genes in normal kidneys and in renal cell carcinomas (RCC). We identified a number of genes, including CXCR4, matrix metalloproteinase 9, thrombospondin 2, and vascular endothelial growth factor, that were highly expressed in RCC versus normal tissue. One gene, hevin, appears to be selectively upregulated in RCC in contrast to downregulation of this gene in lung and colon tumors. This approach provides a powerful means to identify potential markers of tumor vascularization.

Keywords:
Angiogenesis, Endothelium, Hevin, Chemokines, Extracellular matrix, Carcinoma, Kidney
1.
Burgess JK: Gene expression studies using microarrays. Clin Exp Pharmacol Physiol 2001;28:321–328.
2.
Byers RJ, Hoyland JA, Dixon J, Freemont AJ: Subtractive hybridization – genetic takeaways and the search for meaning. Int J Exp Pathol 2000;81:391–404.
3.
Cooper CS: Applications of microarray technology in breast cancer research. Breast Cancer Res 2001;3:158–175.
4.
Cunningham MJ: Genomics and proteomics: The new millennium of drug discovery and development. J Pharmacol Toxicol Methods 2000;44:291–300.
5.
Deyholos MK, Galbraith DW: High-density microarrays for gene expression analysis. Cytometry 2001;43:229–238.
6.
Dopazo J, Zanders E, Dragoni I, Amphlett G, Falciani F: Methods and approaches in the analysis of gene expression data. J Immunol Methods 2001;250:93–112.
7.
Geschwind DH: Sharing gene expression data: An array of options. Nat Rev Neurosci 2001;2:435–438.
8.
Herrmann JL, Rastelli L, Burgess CE, Fernandez EE, Rothberg BE, Rothberg JM, Shimkets RA: Implications of oncogenomics for cancer research and clinical oncology. Cancer J 2001;7:40–51.
9.
Polyak K, Riggins GJ: Gene discovery using the serial analysis of gene expression technique: Implications for cancer research. J Clin Oncol 2001;19:2948–2958.
10.
Quackenbush J: Computational analysis of microarray data. Nat Rev Genet 2001;2:418–427.
11.
Steinmetz LM, Davis RW: High-density arrays and insights into genome function. Biotechnol Genet Eng Rev 2000;17:109–146.
12.
Triche TJ, Schofield D, Buckley J: DNA microarrays in pediatric cancer. Cancer J 2001;7:2–15.
13.
Werner T: Cluster analysis and promoter modelling as bioinformatic tools for the identification of target genes from expression array data. Pharmacogenomics 2001;2:25–36.
14.
Peale FV Jr, Gerritsen ME: Gene profiling techniques and their application in angiogenesis and vascular development. J Pathol 2001;195:7–19.
15.
Nanus DM, Schmitz-Drager BJ, Motzer RJ, Lee AC, Vlamis V, Cordon-Cardo C, Albino AP, Reuter VE: Expression of basic fibroblast growth factor in primary human renal tumors: Correlation with poor survival. J Natl Cancer Inst 1993;85:1597–1599.
16.
Fujimoto K, Ichimori Y, Kakizoe T, Okajima E, Sakamoto H, Sugimura T, Terada M: Increased serum levels of basic fibroblast growth factor in patients with renal cell carcinoma. Biochem Biophys Res Commun 1991;180:386–392.
17.
Takahashi A, Sasaki H, Kim SJ, Tobisu K, Kakizoe T, Tsukamoto T, Kumamoto Y, Sugimura T, Terada M: Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res 1994;54:4233–4237.
18.
Nicol D, Hii SI, Walsh M, Teh B, Thompson L, Kennett C, Gotley D: Vascular endothelial growth factor expression is increased in renal cell carcinoma. J Urol 1997;157:1482–1486.
19.
Kugler A, Hemmerlein B, Thelen P, Kallerhoff M, Radzun HJ, Ringert RH: Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma. J Urol 1998;160:1914–1918.
20.
Lein M, Jung K, Laube C, Hübner T, Winkelmann B, Stephan C, Hauptmann S, Rudolph B, Schnorr D, Loening SA: Matrix-metalloproteinases and their inhibitors in plasma and tumor tissue of patients with renal cell carcinoma. Int J Cancer 2000;85:801–804.
21.
Wechsel HW, Bichler KH, Feil G, Loeser W, Lahme S, Petri E: Renal cell carcinoma: Relevance of angiogenetic factors. Anticancer Res 1999;19:1537–1540.
22.
Katagiri A, Watanabe R, Tomita Y: E-cadherin expression in renal cell cancer and its significance in metastasis and survival. Br J Cancer 1995;71:376–379.
23.
Knebelmann B, Ananth S, Cohen HT, Sukhatme VP: Transforming growth factor alpha is a target for the von Hippel-Lindau tumor suppressor. Cancer Res 1998;58:226–231.
24.
Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999;399:271–275.
25.
Nakagawa M, Emoto A, Hanada T, Nasu N, Nomura Y: Tubulogenesis by microvascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma. Br J Urol 1997;79:681–687.
26.
Nikitenko LL, MacKenzie I, Rees MC, Bicknell R: Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium. Mol Hum Reprod 2000;6:811–819.
27.
Rempel SA, Dudas S, Ge S, Gutierrez JA: Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Clin Cancer Res 2000;6:102–111.
28.
Koshiba T, Hosotani R, Miyamoto Y, Ida J, Tsuji S, Nakajima S, Kawaguchi M, Kobayashi H, Doi R, Hori T, Fujii N, Imamura M: Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: A possible role for tumor progression. Clin Cancer Res 2000;6:3530–3535.
29.
Hawighorst T, Velasco P, Streit M, Hong YK, Kyriakides TR, Brown LF, Bornstein P, Detmar M: Thrombospondin-2 plays a protective role in multistep carcinogenesis: A novel host anti-tumor defense mechanism. Embo J 2001;20:2631–2640.
30.
Kahn J, Mehraban F, Ingle G, Xin X, Bryant J, Vehar G, Schoenfeld J, Grimaldi C, Peale F, Drakharapu A, Lewin D, Gerritsen M: Gene expression profiling in an in vitro model of angiogenesis. Am J Pathol 2000;156:1887–1900.
31.
Fujiwara Y, Sugita Y, Nakamori S, Miyamoto A, Shiozaki K, Nagano H, Sakon M, Monden M: Assessment of Stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers. Int J Oncol 2000;16:799–804.
32.
Claeskens A, Ongenae N, Neefs JM, Cheyns P, Kaijen P, Cools M, Kutoh E: Hevin is down-regulated in many cancers and is a negative regulator of cell growth and proliferation. Br J Cancer 2000;82:1123–1130.
© 2002 S. Karger AG, Basel
2002
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