Malignant mesothelioma-associated inflammatory microenvironment promotes tumor progression via GPNMB DOI Creative Commons
Cristina Belgiovine, Elisabeth Digifico, Marco Erreni

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 18, 2025

Tumor-Associated Macrophages (TAMs) are the main immune component of tumor stroma with heterogeneous functional activities, predominantly suppressing response and promoting progression, also via secretion different factors. Among these, GPNMB (Glycoprotein non-metastatic B) is usually associated disease progression in several types. Malignant pleural mesothelioma (MPM) a severe neoplasia poor prognosis, characterized by an abundancy TAMs, testifying presence long-lasting inflammation which pathogenetic disease. However, role MPM unclear. Clinical samples from patients were used to measure RNA protein levels GPNMB. The vivo was studied orthotopic mouse model using murine cell lines AB1 AB22. Experiments included growth wild type GPNMB-deficient mice blocking GPNMB-induced signaling anti-CD44 antibodies. We show that human tissues mainly produced infiltrating TAMs. Gpnmb TCGA significantly lower survival. Using we observed GPNMB-defective (DBA2/J mice) unable produce protein, tumors formed AB22 cells grow less than GPNMB-proficient (DBA2/J-Gpnmb+ mice), indicating host involved progression. Likewise, ectopic expression causes acceleration vivo, compared mock-transduced cells. Treatment tumor-bearing (a major receptor for GPNMB) results significant reduction growth. Overall, these indicate GPNMB, product marker gene driver may constitute promising therapeutic target.

Язык: Английский

Malignant mesothelioma-associated inflammatory microenvironment promotes tumor progression via GPNMB DOI Creative Commons
Cristina Belgiovine, Elisabeth Digifico, Marco Erreni

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 18, 2025

Tumor-Associated Macrophages (TAMs) are the main immune component of tumor stroma with heterogeneous functional activities, predominantly suppressing response and promoting progression, also via secretion different factors. Among these, GPNMB (Glycoprotein non-metastatic B) is usually associated disease progression in several types. Malignant pleural mesothelioma (MPM) a severe neoplasia poor prognosis, characterized by an abundancy TAMs, testifying presence long-lasting inflammation which pathogenetic disease. However, role MPM unclear. Clinical samples from patients were used to measure RNA protein levels GPNMB. The vivo was studied orthotopic mouse model using murine cell lines AB1 AB22. Experiments included growth wild type GPNMB-deficient mice blocking GPNMB-induced signaling anti-CD44 antibodies. We show that human tissues mainly produced infiltrating TAMs. Gpnmb TCGA significantly lower survival. Using we observed GPNMB-defective (DBA2/J mice) unable produce protein, tumors formed AB22 cells grow less than GPNMB-proficient (DBA2/J-Gpnmb+ mice), indicating host involved progression. Likewise, ectopic expression causes acceleration vivo, compared mock-transduced cells. Treatment tumor-bearing (a major receptor for GPNMB) results significant reduction growth. Overall, these indicate GPNMB, product marker gene driver may constitute promising therapeutic target.

Язык: Английский

Процитировано

0