Cellular and molecular parameters of mesothelioma.
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.
Ramos-Nino
Maria E
ME
Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. Maria.Ramos@uvm.edu
Testa
Joseph R
JR
Altomare
Deborah A
DA
Pass
Harvey I
HI
Carbone
Michele
M
Bocchetta
Maurizio
M
Mossman
Brooke T
BT
D000818:Animals; D001194:Asbestos / Q000009:adverse effects*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D006801:Humans; D008654:Mesothelioma / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D010534:Peritoneal Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D010997:Pleural Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D013539:Simian virus 40; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy
D001194:Asbestos