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Cancers as Wounds that Do Not Heal: Differences and Similarities between Renal Regeneration/Repair and Renal Cell Carcinoma

¹ Laboratory of Biosystems and Cancer, ² Comparative Oncology Program, ³ Laboratory of Population Genetics, ⁴ Laboratory of Pathology, ⁵ Metabolism Branch, ⁶ Genomics & Bioinformatics Group, Laboratory of Molecular Pharmacology, ⁷ Urologic Oncology Branch, Center for Cancer Research, ⁸ Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, ⁹ Bioinformatics and Molecular Analysis Section, Computational Bioscience and Engineering Laboratory, Center for Information Technology, ¹⁰ Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland; and ¹¹ Hebrew University-Hadassah Medical School, Jerusalem, Israel

Requests for reprints: Joseph Riss, Wound Healing and Oncogenesis, Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, NIH, Building 37/Room 5032, 37 Convent MSC 4264, Bethesda, MD 20892. Phone: 301-402-7203; Fax: 301-480-2772; E-mail: rissjo{at}mail.nih.gov.

Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia. (Cancer Res 2006; 66(14): 7216-24)

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