Cellular and molecular parameters of mesothelioma

Our plain-English summary of Cellular and molecular parameters of mesothelioma, by M.E. Ramos-Nino, J.R. Testa, D.A. Altomare, et al (Journal of Cellular Biochemistry, 2006).

The study

• Authors: M.E. Ramos-Nino, J.R. Testa, D.A. Altomare, H.I. Pass, M. Carbone, M. Bocchetta, B.T. Mossman
• Journal: Journal of Cellular Biochemistry
• Published: 2006;98(4):723-34
• Type of article: Review
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

2006 Wiley-Liss, Inc.

In plain English

This article was a review, not a new study. The authors summarized published research on the causes and biology of malignant mesothelioma, a cancer of the lining of the body cavities, most often the pleura and peritoneum. They wrote that in the US the most important cause is occupational asbestos exposure, primarily the amphiboles crocidolite and amosite. Whether chrysotile alone causes mesothelioma remains controversial. They described evidence that genetic susceptibility and simian virus 40 (SV40) may also contribute. One study they cited reported a risk 27-fold higher with SV40 infection plus asbestos exposure than with asbestos exposure alone. They reviewed gene deletions, cell signaling triggered by asbestos and SV40, and work from their own laboratories. This included asbestos-treated heterozygous Nf2 knockout mice that showed molecular features of the human disease. They described two possible blood markers. The first, soluble mesothelin-related protein, was reported in one study to mark mesothelioma with 83% sensitivity and 95% specificity in 48 patients. The second was osteopontin. The authors concluded that this knowledge may improve screening, diagnosis and treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review (a 'Prospects' article) of published research on the causes and molecular biology of malignant mesothelioma, including some of the authors' own laboratory work
• Who was studied: No study population of its own. The authors reviewed published human, animal and cell-culture research on malignant mesothelioma.
• Exposure: Asbestos (amphiboles crocidolite and amosite; chrysotile; tremolite and other amphiboles), erionite, and simian virus 40 (SV40) infection
• Main results:
  • The authors wrote that the link between amphibole asbestos and mesothelioma is well documented. They wrote that the cancer-causing potential of chrysotile alone, or with negligible amphibole contamination, remains controversial.
  • According to studies the authors cited (Carbone, 1999; Klein et al., 2002), approximately half of mesotheliomas in the US are positive for SV40 large T antigen.
  • The authors described an epidemiologic report (Porta et al., 2005) with three findings: asbestos exposure alone was associated with mesothelioma; SV40 alone was not; and SV40 infection plus asbestos exposure showed a risk 27-fold higher than asbestos exposure alone.
  • The authors reported that their group showed that heterozygous Nf2 knockout mice treated with asbestos reproduced molecular features of human mesothelioma.
  • The authors reported that their group found the AKT pathway frequently activated in mesotheliomas. They found that inhibiting this pathway inhibited cell growth and increased sensitivity to conventional chemotherapy drugs.
  • A study the authors cited (Robinson et al., 2005) reported that serum soluble mesothelin-related protein (SMRP) marked mesothelioma with 83% sensitivity and 95% specificity in 48 mesothelioma patients tested. SMRP was elevated in 75% of patients at diagnosis.
  • A study the authors cited (Pass et al., 2005) measured serum osteopontin in three groups totaling 190 patients: asbestos-exposed people without cancer, unexposed people without cancer, and asbestos-exposed patients with pleural mesothelioma. Osteopontin levels could distinguish the asbestos-exposed people who had mesothelioma.
  • In a cited study of 181 tissue samples (Gordon et al., 2002, 2003), gene expression ratios correctly identified 95% and 99% of the two sets of tumors (mesothelioma versus lung adenocarcinoma).
  • A cited study (Pass et al., 2004) reported that gene expression profiles in pleural mesothelioma predicted time to progression and survival with 76% to 95.2% accuracy, using 27 classifiers.
• The authors' conclusion: The authors concluded that growing knowledge of mesothelioma biology may lead to improvements in screening, diagnosis and therapy. They added that understanding the pathways involved will help design targeted treatments.
• Limitations the authors state:
  • The authors noted that studies of transient worker populations, who may be exposed to different fiber types over a lifetime, are difficult to interpret.
  • The authors noted that relatively little is known about the critical genetic changes that lead to mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Neoplasm, Mesothelial Cells, Asbestos Exposure, SV40, Chemotherapy, Prognosis.

Related studies

• Simian virus 40 transformation, malignant mesothelioma and brain tumors — F. Qi, M. Carbone, et al. (2011)
• SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study — A. Cristaudo, R. Foddis, et al. (2005)
• Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection — M. Suzuki, S. Toyooka, et al. (2005)
• Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids — F. López-Ríos, P.B. Illei, et al. (2004)
• SV40 multiple tissue infection and asbestos exposure in a hyperendemic area for malignant mesothelioma — M. Comar, C. Rizzardi, et al. (2007)
• Simian virus 40 sequences in blood specimens from healthy individuals of Casale Monferrato, an industrial town with a history of asbestos pollution — C. Pancaldi, V. Balatti, et al. (2009)

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