Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells
Abstract
Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in therapy resistance are still insufficient. We analyzed SERPINA1 mRNA expression in three different multidrug-resistant (MDR) cell lines—U87-TxR, NCI-H460/R, and DLD1-TxR—and in U87 cells grown in alginate microfibers as a 3D cellular model of glioblastoma. Expression of IL-6 as a major modulator of SERPINA1 was also analyzed. Additionally, AAT protein expression in MDR cells was analyzed by immunofluorescence. SERPINA1 gene expression and AAT protein expression were significantly upregulated in all the tested MDR cell lines compared with their sensitive counterparts. Moreover, SERPINA1 was sig...nificantly upregulated in 3D models of glioblastoma, previously found to have upregulated drug-resistance-related gene expression compared with 2D cells. With the exception of NCI-H460/R, in all cell lines as well as in a 3D model of U87 cells, increase in SERPINA1 expression correlated with the increase in IL-6 expression. Our results indicate that AAT could be utilized as a biomarker of therapy resistance in cancer; however, further studies are needed to elucidate the mechanisms driving AAT upregulation in therapy resistance and its biological significance in this process.
Keywords:
Alpha-1 antitrypsin / Cancer / Chemoresistance / SERPINA1 / Therapy resistanceSource:
Histochemistry and Cell Biology, 2023, 159, 5, 431-437Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Divac Rankov, Aleksandra AU - Jovanović Stojanov, Sofija AU - Dragoj, Miodrag AU - Ljujić, Mila PY - 2023 UR - https://doi.org/10.1007/s00418-022-02172-3 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2243 AB - Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in therapy resistance are still insufficient. We analyzed SERPINA1 mRNA expression in three different multidrug-resistant (MDR) cell lines—U87-TxR, NCI-H460/R, and DLD1-TxR—and in U87 cells grown in alginate microfibers as a 3D cellular model of glioblastoma. Expression of IL-6 as a major modulator of SERPINA1 was also analyzed. Additionally, AAT protein expression in MDR cells was analyzed by immunofluorescence. SERPINA1 gene expression and AAT protein expression were significantly upregulated in all the tested MDR cell lines compared with their sensitive counterparts. Moreover, SERPINA1 was significantly upregulated in 3D models of glioblastoma, previously found to have upregulated drug-resistance-related gene expression compared with 2D cells. With the exception of NCI-H460/R, in all cell lines as well as in a 3D model of U87 cells, increase in SERPINA1 expression correlated with the increase in IL-6 expression. Our results indicate that AAT could be utilized as a biomarker of therapy resistance in cancer; however, further studies are needed to elucidate the mechanisms driving AAT upregulation in therapy resistance and its biological significance in this process. T2 - Histochemistry and Cell Biology T1 - Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells EP - 437 IS - 5 SP - 431 VL - 159 DO - 10.1007/s00418-022-02172-3 ER -
@article{ author = "Divac Rankov, Aleksandra and Jovanović Stojanov, Sofija and Dragoj, Miodrag and Ljujić, Mila", year = "2023", abstract = "Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in therapy resistance are still insufficient. We analyzed SERPINA1 mRNA expression in three different multidrug-resistant (MDR) cell lines—U87-TxR, NCI-H460/R, and DLD1-TxR—and in U87 cells grown in alginate microfibers as a 3D cellular model of glioblastoma. Expression of IL-6 as a major modulator of SERPINA1 was also analyzed. Additionally, AAT protein expression in MDR cells was analyzed by immunofluorescence. SERPINA1 gene expression and AAT protein expression were significantly upregulated in all the tested MDR cell lines compared with their sensitive counterparts. Moreover, SERPINA1 was significantly upregulated in 3D models of glioblastoma, previously found to have upregulated drug-resistance-related gene expression compared with 2D cells. With the exception of NCI-H460/R, in all cell lines as well as in a 3D model of U87 cells, increase in SERPINA1 expression correlated with the increase in IL-6 expression. Our results indicate that AAT could be utilized as a biomarker of therapy resistance in cancer; however, further studies are needed to elucidate the mechanisms driving AAT upregulation in therapy resistance and its biological significance in this process.", journal = "Histochemistry and Cell Biology", title = "Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells", pages = "437-431", number = "5", volume = "159", doi = "10.1007/s00418-022-02172-3" }
Divac Rankov, A., Jovanović Stojanov, S., Dragoj, M.,& Ljujić, M.. (2023). Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells. in Histochemistry and Cell Biology, 159(5), 431-437. https://doi.org/10.1007/s00418-022-02172-3
Divac Rankov A, Jovanović Stojanov S, Dragoj M, Ljujić M. Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells. in Histochemistry and Cell Biology. 2023;159(5):431-437. doi:10.1007/s00418-022-02172-3 .
Divac Rankov, Aleksandra, Jovanović Stojanov, Sofija, Dragoj, Miodrag, Ljujić, Mila, "Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells" in Histochemistry and Cell Biology, 159, no. 5 (2023):431-437, https://doi.org/10.1007/s00418-022-02172-3 . .