| Abstract |
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 secreted 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.
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