Aberrant splicing and protease involvement in mesothelin release from epithelioid mesothelioma cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Science Année : 2008

Aberrant splicing and protease involvement in mesothelin release from epithelioid mesothelioma cells

Carole Sapede
Anne Gauvrit
  • Fonction : Auteur
Isabelle Barbieux
  • Fonction : Auteur
Martine Padieu
  • Fonction : Auteur
Laurent Cellerin
  • Fonction : Auteur
Christine Sagan
  • Fonction : Auteur
Arnaud Scherpereel
  • Fonction : Auteur
Gérard Dabouis
  • Fonction : Auteur
Marc Grégoire
  • Fonction : Auteur

Résumé

Elevated amounts of soluble mesothelin‐related proteins (SMRP) have already been reported in sera and pleural effusions from mesothelioma patients, providing a useful diagnostic marker for malignant pleural mesothelioma (MPM). However, the origin of SMRP is not yet understood. Production of SMRP could be related to abnormal splicing events leading to synthesis of a secreted protein (release) or to an enzymatic cleavage from membrane‐bound mesothelin (ectodomain shedding). To test these hypotheses, we used a panel of mesothelioma cells established in culture from pleural effusions of MPM patients. Our in vitro results confirmed specific mesothelin expression and SMRP production in supernatants from epithelioid MPM cell lines, thus providing a relevant cellular model to study soluble mesothelin production mechanisms. The expression of mesothelin‐encoding RNA variants was screened by reverse transcription–polymerase chain reaction experiments. Protease involvement in mesothelin cleavage from the cellular surface was investigated by treatment of MPM cells with GM6001, a broad‐spectrum MMP‐ and ADAM‐family inhibitor. GM6001 treatment significantly impaired SMRP production by MPM cell lines, in favor of an enzymatic‐mediated shedding process. In addition, a splice variant transcript of mesothelin (variant 3) was detected in these MPM cell lines, in accordance with the release of a secreted part of the protein. Our results indicate that both mechanisms could be implicated in soluble mesothelin production by epithelioid mesothelioma cells. ( Cancer Sci 2008; 99: 590–594)

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Cancer
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Dates et versions

hal-04636462 , version 1 (05-07-2024)

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Carole Sapede, Anne Gauvrit, Isabelle Barbieux, Martine Padieu, Laurent Cellerin, et al.. Aberrant splicing and protease involvement in mesothelin release from epithelioid mesothelioma cells. Cancer Science, 2008, 99 (3), pp.590-594. ⟨10.1111/j.1349-7006.2007.00715.x⟩. ⟨hal-04636462⟩
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