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All-trans-retinoic acid inhibits tumour growth of malignant pleural mesothelioma in mice
- Source :
- European Respiratory Journal. 34:1159-1167
- Publication Year :
- 2009
- Publisher :
- European Respiratory Society (ERS), 2009.
-
Abstract
- Malignant pleural mesothelioma (MPM) is an aggressive malignant tumour of mesothelial origin associated with asbestos exposure. Because MPM has limited response to conventional chemotherapy and radiotherapy, the prognosis is very poor. Several researchers have reported that cytokines such as interleukin (IL)-6 play an important role in the growth of MPM. Previously, it was reported that all-trans-retinoic acid (ATRA) inhibited the production and function of IL-6 and transforming growth factor (TGF)-beta1 in experiments using lung fibroblasts. We investigated whether ATRA had an inhibitory effect on the cell growth of MPM, the origin of which was mesenchymal cells similar to lung fibroblasts, using a subcutaneous xenograft mouse model. We estimated the tumour growth and performed quantitative measurements of IL-6, TGF-beta1 and platelet-derived growth factor (PDGF) receptor (PDGFR)-beta mRNA levels both of cultured MPM cells and cells grown in mice with or without the administration of ATRA. ATRA significantly inhibited MPM tumour growth. In vitro studies disclosed that the administration of ATRA reduced 1) mRNA levels of TGF-beta1, TGF-beta1 receptors and PDGFR-beta, and 2) TGF-beta1-dependent proliferation and PDGF-BB-dependent migration of MPM cells. These data may provide a rationale to explore the clinical use of ATRA for the treatment of MPM.
- Subjects :
- Mesothelioma
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Pleural Neoplasms
medicine.medical_treatment
Becaplermin
Tretinoin
Mice, SCID
Receptor, Platelet-Derived Growth Factor beta
Transforming Growth Factor beta1
Mice
Pleural disease
Cell Movement
Cell Line, Tumor
medicine
Animals
RNA, Messenger
neoplasms
Cell Proliferation
Platelet-Derived Growth Factor
biology
Interleukin-6
Cell growth
business.industry
Growth factor
Asbestos
Proto-Oncogene Proteins c-sis
medicine.disease
Cytokine
biology.protein
Cancer research
Female
business
Neoplasm Transplantation
Platelet-derived growth factor receptor
medicine.drug
Transforming growth factor
Subjects
Details
- ISSN :
- 13993003 and 09031936
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- European Respiratory Journal
- Accession number :
- edsair.doi.dedup.....edb4a0fad42cdd2e9bc81156ee624f2b