Biological and immunological aspects of malignant mesothelioma.
Malignant mesothelioma (MM) is an aggressive tumour, which is strongly associated with previous asbestos exposure and is resistant to all conventional anticancer therapies. An understanding of the biological properties of MM may provide insights into useful therapeutic strategies, and MM cell lines and animal models have been major contributors to our current knowledge of this tumour. Although karyotypic abnormalities are frequent, there is no clear evidence of a mesothelioma-specific chromosomal aberration. Similarly, there is no evidence of activation or over-expression of a known oncogene, or of the inactivation of currently identified tumour suppressor genes. A number of growth factors, including platelet derived growth factors A and B (PDGF-A and -B), insulin-like growth factor I and transforming growth factor-beta (TGF-beta), and some of their receptors, have been reported to be expressed by MM cells, and each has the potential to play a role as a growth stimulant for MM or to modify immune responses to the tumour. Some data support an autocrine role for PDGF-A. MM cell lines are susceptible to lysis by a variety of immune effector cells, and their growth can often be inhibited by cytokines. The possibility of stimulating an immune response to MM by genetic manipulation of the tumour cells has been investigated using a murine model. The data so far suggest that transfection of allogeneic class I major histocompatibility complex genes or syngeneic class II genes alone is unlikely to induce protective immunity.(ABSTRACT TRUNCATED AT 250 WORDS)
Garlepp
M J
MJ
Australian Neuromuscular Research Institute, University of Western Australia, QEII Medical Centre, Nedlands.
Leong
C C
CC
D000818:Animals; D001194:Asbestos / Q000009:adverse effects; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008654:Mesothelioma / Q000235:genetics / Q000276:immunology; D009857:Oncogenes; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000276:immunology; D010997:Pleural Neoplasms / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes; D014162:Transfection; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D001194:Asbestos