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-I 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.
|Number of pages||6|
|Journal||British Journal of Cancer|
|State||Published - 21 Jul 2003|
Bibliographical noteFunding Information:
This work was supported by the Arison Family. G. Rechavi holds the Gregorio and Dora Shapiro Chair in Hematologic Malignancies at the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Ofer Margalit, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
- B16-F10.9 melanoma
- D122 Lewis lung carcinoma
- DNA microarrays
- Gene expression