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Malignant mesothelioma (MM) is an aggressive tumor that frequently spread thoracic cavity. In addition, since it is refractory to conventional chemotherapy and radiotherapy, prognosis of patients with MM is very limited. To clarify the molecular pathogenesis of MM and develop novel, more effective therapeutic modalities, experimental animal models which resemble clinical behavior of MM are indispensable. Here, we report orthotopic-implantation SCID-mouse model of human MM cells. In the present study, we used two human MM cell lines, named EHMES-1 and EHMES-10, established from two different patients. EHMES-10 cells secreated 10 times higher level of vascular endothelial growth factor (VEGF) protein compared with EHMES-1 cells. Both two cell lines overexpressed epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2). When MM cells were inoculated into thoracic cavity (orthotopic site) of SCID mice, EHMES-1 cells did not produce any tumors or pleural effusions by day 84. On the other hand, EHMES-10 cells reproducibly produced tumors (2-5 mm in diameter) accompanying with pleural dissemination and bloody pleural effusions (up to 1ml/mouse) by day 35. Treatment of EHMES-10-bearing SCID mice with cisplatin or gemcitabine, those are considered as effective chemotherapeutic agents for MM patients, on day 7 inhibited production of pleural tumors and pleural effusion. These results suggest that pattern of progression and chemosensitivity of orthotopically implanted EHMES-10 cells resemble those of MM patients. Therefore, our patient-like orthotopic model with EHMES-10 cells may be useful for examining molecular pathogenesis and contribute to develop the novel treatment strategy for MM.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]