1. ¹Pediatric Hemato-Oncology, Safra Children's Hospital, Sheba Medical Center, Affiliated to Tel-Aviv University, Tel Hashomer 52621, Israel
2. ²Functional Genomics unit, Sheba Medical Center, Affiliated to Tel-Aviv University, Tel Hashomer 52621, Israel
3. ³Weizmann Institute of Science, PO Box 26, Rehovot 76100, Israel
4. ⁴Institute of Medical Oncology and Radiotherapy, Sheba Medical Center, Affiliated to Tel-Aviv University, Tel Hashomer 52621, Israel
5. ⁵Department of Molecular Genetics, Felsenstein Medical Research Center, Rabin Medical Center, 14 Kaplan street, Petah-Tikva 49100, Israel

Correspondence: O Margalit, Pediatric Hemato-Oncology, Safra Children's Hospital, Sheba Medical Center, Affiliated to Tel-Aviv University, Tel Hashomer 52621, Israel. E-mail: ofer.margalit@sheba.health.gov.il

Received 20 September 2002; Accepted 18 March 2003.

Abstract

Despite advances in the management of solid tumours, the development of metastases continues to be the most significant problem and cause of death for cancer patients. To define genetic determinants of pulmonary metastases, we have applied oligonucleotide microarrays to established murine models of highly metastatic D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines. These models are characterised by primary subcutaneous growth in C57BL/6J mice, a period of minimal residual disease and spontaneous pulmonary metastases. Microarray analysis defined seven genes, namely – arginase, brain natriuretic peptide (BNP), interleukin-1 alpha (IL-1 alpha), plasminogen activator inhibitor-2 (PAI-2), surfactant protein C (SP-C), uteroglobin (UG) and wnt-1-induced secreted protein-1 (WISP-1), which were consistently elevated in pulmonary metastases compared to the primary tumour of both D122 and B16-F10.9 models. Previous studies demonstrated that two of these seven genes, IL-1 alpha and PAI-2, are involved in the metastatic process. The results obtained by the microarrays were confirmed by real-time quantitative PCR, for three chosen genes – PAI-2, WISP-1 and UG. Our approach aimed to identify genes essential for the metastatic process in general and for pulmonary metastases specifically. Further research should address the precise role of these genes in the metastasising process to the lungs and test if they could be used as targets for future therapies.