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Review
. 2006 Jul 1;98(4):723-34.
doi: 10.1002/jcb.20828.

Cellular and molecular parameters of mesothelioma

Maria E Ramos-Nino  1 , Joseph R Testa, Deborah A Altomare, Harvey I Pass, Michele Carbone, Maurizio Bocchetta, Brooke T Mossman
Affiliations
Review

Cellular and molecular parameters of mesothelioma

Maria E Ramos-Nino et al. J Cell Biochem. .

Abstract

Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high-throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin-related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors.

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Figures

Fig. 1
Fig. 1
Morphology of chrysotile (A) and crocidolite (B) asbestos fibers as illustrated by scanning electron microscopy. Arrow in A shows a long chrysotile fiber on the plasma membrane and arrowhead shows short fiber bundles.
Fig. 2
Fig. 2
A schema indicating cell signaling pathways and outcomes in mesothelial cells that are triggered by asbestos fibers or associated with SV40 infection. SV40, Simian virus 40; SV40 tag, SV40 small t antigen; SV40 Tag, SV40 large T antigen; PI3K, phosphatidylinositol 3-kinase; MEK, mitogen activated protein (MAP)/ERK kinase; ERK, extracellular signal regulated protein kinase; Rb, retinoblastoma; AP-1, activator protein-1; NFκB, nuclear factor kappa-B; RASSF1A, ras association domain family 1A; RTK, receptor tyrosine kinases; EGFR, epidermal growth factor receptor; PP2A, protein serine/threonine phosphatase 2A.
See this image and copyright information in PMC

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