Restored expression of the MYO18B gene suppresses orthotopic growth and the production of bloody pleural effusion by human malignant pleural mesothelioma cells in SCID mice.
Malignant pleural mesothelioma (MPM) is closely related to exposure to asbestos, and a rapid increase in the number of MPM patients is therefore estimated to occur from 2010 to 2040 in Japan. Because MPM is refractory to conventional chemotherapy and radiotherapy, the prognosis of MPM patients is extremely poor. MYO18B, a novel member of the myosin family, is a tumor suppressor gene isolated from a homozygously deleted region at 22q12.1 in a lung cancer cell line. The inactivation of the MYO18B gene plays an important role in several malignant diseases. However, the role of MYO18B in the progression of MPM is still unknown. Six different human MPM cell lines were used in this study. Western blot revealed that none of the cell lines expressed a detectable level of MYO18B protein. One of the MPM cell lines, EHMES-10, was transfected with the MYO18B gene. We found that a restored expression of the MYO18B protein in EHMES-10 cells resulted in the inhibition of their anchorage-independent growth and motility in vitro. In addition, it also inhibited their ectopic (subcutaneous space) and orthotopic (thoracic cavity) growth in SCID mice, in association with an increased degree of cell apoptosis. Furthermore, it also suppressed the production of bloody pleural effusion after orthotopic injection. These findings suggest that the restored expression of MYO18B may be a useful therapeutic strategy for the treatment of locally advanced MPM in humans.
Edakuni
Nobutaka
N
Department of Internal Medicine and Molecular Therapeutics, University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Ikuta
Kenji
K
Yano
Seiji
S
Nakataki
Emiko
E
Muguruma
Hiroaki
H
Uehara
Hisanori
H
Tani
Masachika
M
Yokota
Jun
J
Aizawa
Hisamichi
H
Sone
Saburo
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009218:Myosins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010996:Pleural Effusion / Q000235:genetics* / Q000378:metabolism; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
C500982:MYO18B protein, human; D025521:Tumor Suppressor Proteins; D009218:Myosins