In vitro experimental models of mesothelioma revisited

Our plain-English summary of In vitro experimental models of mesothelioma revisited, by A. Singh, N. Pruett, C.D. Hoang (Translational Lung Cancer Research, 2017).

The study

• Authors: A. Singh, N. Pruett, C.D. Hoang
• Journal: Translational Lung Cancer Research
• Published: 2017;6(3):248-258
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a biologically unusual, highly aggressive cancer that defies current multimodality treatments. Epidemiologic data suggest that this malignancy has not abated despite increasingly strict environmental regulations on asbestos, the putative causative agent for sporadic cases. An incomplete understanding of all the factors mechanistically driving mesothelioma is largely responsible for the current lack of curative treatments. Many approaches have been employed to ascertain the step-by-step molecular events involved in mesothelioma oncogenesis including in vitro, small animal in vivo, and human experimental models; though clearly defined, druggable mechanisms still are elusive. Importantly, the foundation of the latest accepted model of tumor initiation is derived from in vitro systems. A thorough review of in vitro mesothelioma oncogenesis models may suggest further opportunities for discovery.

In plain English

This article is a review, not a new experiment. The authors looked at laboratory (in vitro) models that try to recreate how malignant pleural mesothelioma starts by turning human mesothelial cells into cancer-like cells. Their table lists 11 such models published from 1989 to 2014. In the studies reviewed, Lechner and colleagues found these cells highly sensitive to being killed by all asbestos fiber forms tested. Bertino and colleagues reported that low doses of erionite, an asbestos-like zeolite fiber, transformed the cells. Under the same conditions amosite and chrysotile did not transform them, though both killed many cells. Qi and colleagues reported that crocidolite or chrysotile could transform the cells when the inflammatory signal TNF-α helped them survive. The authors noted that most models took at least 4 to 16 weeks to show transformation. They also noted that transformation lacked a precise definition and that none of the starting cells were truly normal. The authors concluded that these models have added to understanding of mesothelioma, but molecular mechanisms remain to be resolved.

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 of in vitro (laboratory cell culture) models of mesothelioma development
• Who was studied: No people were studied. The review covered laboratory models using human mesothelial cells (the MeT-5A cell line, LP-9 cells, and primary cells from pleural fluid or tissue). Its table lists 11 models published from 1989 to 2014.
• Exposure: The reviewed models used several agents: asbestos fibers (amosite, crocidolite, chrysotile), erionite, simian virus 40 (SV40), inflammatory cytokines, macrophage co-culture, single-walled carbon nanotubes, Chlamydia pneumoniae, and gene transfer
• Main results:
  • Lechner et al. (reviewed study): human mesothelial cells were highly sensitive to the cytotoxic (cell-killing) effects of all asbestos fiber forms tested
  • Bocchetta et al. (reviewed study): in human mesothelial cells, the combination of asbestos and SV40 produced the most foci of transformed cells
  • Bertino et al. (reviewed study): amosite and chrysotile did not transform human mesothelial cells under the conditions in which erionite did, but they caused extensive cell killing
  • Qi et al. (reviewed study): human mesothelial cells needed TNF-α to survive asbestos; with it, either crocidolite or chrysotile could transform the cells
  • Wang et al. (reviewed study): erionite alone did not transform MeT-5A cells; transformation required added inflammatory cytokines
  • The authors noted that many human epidemiologic studies do not support a clinically relevant association between SV40 and human pleural mesothelioma
• The authors' conclusion: The authors concluded that, despite caveats, in vitro models have added to understanding of pleural mesothelioma biology, but molecular mechanisms in the accepted model of how it develops remain to be resolved
• Limitations the authors state:
  • Most models showed transformed cells only after long periods of at least 4 to 16 weeks
  • There is no precise definition of cell transformation across the models
  • The starting cells vary and none are truly normal; MeT-5A cells carry SV40 sequences and abnormal ploidy
  • In vitro systems lack the cellular complexity of the original tumor

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Oncogenesis, Discovery.

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