In vitro and in vivo characterization of highly purified human mesothelioma derived cells

Our plain-English summary of In vitro and in vivo characterization of highly purified human mesothelioma derived cells, by A. Melotti, A. Daga, D. Marubbi, et al (BMC Cancer, 2010).

The study

• Authors: A. Melotti, A. Daga, D. Marubbi, A. Zunino, L. Mutti, G. Corte
• Journal: BMC Cancer
• Published: 2010;10:54
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma is a rare disease known to be resistant to conventional therapies. A better understanding of mesothelioma biology may provide the rationale for new therapeutic strategies. In this regard, tumor cell lines development has been an important tool to study the biological properties of many tumors. However all the cell lines established so far were grown in medium containing at least 10% serum, and it has been shown that primary cell lines cultured under these conditions lose their ability to differentiate, acquire gene expression profiles that differ from that of tissue specific stem cells or the primary tumor they derive from, and in some cases are neither clonogenic nor tumorigenic. Our work was aimed to establish from fresh human pleural mesothelioma samples cell cultures maintaining tumorigenic properties.

Methods: The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated.

Results: The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor.

Conclusions: These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma tumor initiating cells.

In plain English

This was a laboratory study, not a study of asbestos exposure. The article does not report the patients' asbestos history. The authors, working in Italy, tried to grow cells from fresh human pleural mesothelioma samples in a low-serum culture medium, aiming for cultures that keep their ability to form tumors. Of 35 tumor samples collected, 17 could be grown in the laboratory. Only four of those formed tumors when injected into the abdomen of immunodeficient mice. All four patients were male, had epithelioid mesothelioma and had never received chemotherapy or radiotherapy. Tumors formed even when only 1,000 cells were injected. Cells passed from mouse to mouse kept forming tumors and showed increased tumor-forming ability. The mouse tumors were strongly positive for calretinin and moderately positive for D2-40, mesothelin and WT-1. In all four cultures, more than 90% of cells carried the markers CD47, CD55 and CD99. The cells expressed high levels of the mesothelin and calretinin genes and had very rearranged chromosomes. The authors concluded the cultures may provide a valuable model to study mesothelioma biology.

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: Laboratory study: cell cultures grown from human tumor samples, plus an animal experiment in which the cells were injected into immunodeficient mice
• Who was studied: 35 malignant pleural mesothelioma samples from patients at hospitals in Brescia and Genova, Italy (dates of collection not given). 17 grew in culture and 4 grew in mice. Those 4 came from male patients with epithelioid mesothelioma who had never had chemotherapy or radiotherapy. The animals used were NOD/SCID immunodeficient mice.
• Exposure: No asbestos or other environmental exposure was studied, and the patients' asbestos exposure is not reported. In the experiments, mice were injected in the abdomen with 1,000 to 1,000,000 cultured mesothelioma cells.
• Main results:
  • Of the 17 cell cultures established from 35 samples, only four (named MM1 to MM4) formed tumors in mice.
  • Injecting as few as 1,000 cells did not reduce the rate at which tumors formed in mice.
  • Cells recovered from mouse tumors and injected into new mice still formed tumors and showed increased tumor-forming ability, with tumors developing in a shorter time.
  • Tumors grown in mice were strongly positive for calretinin and moderately positive for D2-40, mesothelin and WT-1. The authors described this profile as diagnostic for human malignant mesothelioma.
  • In all four cultures, more than 90% of cells were positive for CD47, CD55 and CD99, and between 65 and 95% were positive for CD90 and CD46.
  • The cultures expressed high levels of the genes for the mesothelioma markers mesothelin and calretinin.
  • The chromosomes of all four cultures were very rearranged, and chromosomes 8, 14 and 15 were lost in all four.
• The authors' conclusion: The authors concluded that these mesothelioma cell cultures may provide a valuable laboratory and animal model to study the biology of mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, STEM, Mesothelin, Calretinin, Prognosis.

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