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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.
Alice Melotti, and
Antonio Daga, and
Daniela Marubbi, and
Annalisa Zunino, and
Luciano Mutti, and
Giorgio Corte
October 1998,
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research,
Alice Melotti, and
Antonio Daga, and
Daniela Marubbi, and
Annalisa Zunino, and
Luciano Mutti, and
Giorgio Corte
April 2007,
Zhongguo shi yan xue ye xue za zhi,
Alice Melotti, and
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Giorgio Corte
January 2019,
PloS one,
Alice Melotti, and
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Cell death discovery,
Alice Melotti, and
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Annalisa Zunino, and
Luciano Mutti, and
Giorgio Corte
March 2011,
Journal of cellular and molecular medicine,
Alice Melotti, and
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May 2017,
Oncotarget,
Alice Melotti, and
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Methods in molecular biology (Clifton, N.J.),
Alice Melotti, and
Antonio Daga, and
Daniela Marubbi, and
Annalisa Zunino, and
Luciano Mutti, and
Giorgio Corte
January 1987,
In vitro cellular & developmental biology : journal of the Tissue Culture Association,
Alice Melotti, and
Antonio Daga, and
Daniela Marubbi, and
Annalisa Zunino, and
Luciano Mutti, and
Giorgio Corte
May 2003,
Journal of cell science,
Alice Melotti, and
Antonio Daga, and
Daniela Marubbi, and
Annalisa Zunino, and
Luciano Mutti, and
Giorgio Corte
August 2013,
Human gene therapy methods,
