Ukrain affects pancreas cancer cell phenotype in vitro by targeting MMP-9 and intra-/extracellular SPARC expression

Niccola Funel, Francesco Costa, Letizia Pettinari, Adriano Taddeo, Alessandra Sala, Maurizio Chiriva-Internati, Everardo Cobos, Graziano Colombo, Aldo Milzani, Daniela Campani, Isabella Dalle-Donne, Nicoletta Gagliano

Research output: Contribution to journalArticle

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Abstract

Background/Aims: We investigated whether the anticancer drug Ukrain (UK) is able to modulate the expression of some of the key markers of tumor progression in pancreatic cell carcinoma, in order to assess its potential therapeutic effect. Methods: Three cell lines (HPAF-II, PL45, HPAC) were treated with UK (5, 10 and 20 μM) for 48 h, or left untreated. Secreted protein acidic and rich in cysteine (SPARC) mRNA levels were assessed by real-time PCR. Matrix metalloproteinases (MMP)-2 and -9 activity was analyzed by SDS zymography; SPARC protein levels in cell lysates and supernatants were determined by Western blot. Cell cycle was determined by flow cytometric analysis, and invasion by matrigel invasion assay. Results: UK down-regulated MMP-2 and MMP-9, suggesting that UK may decrease pancreatic cancer cell invasion, as confirmed by the matrigel invasion assay. SPARC protein down-regulation in supernatants points to an inhibition by UK of extracellular matrix remodeling in the tumor microenvironment. At the same time, SPARC mRNA and cellular protein level up-regulation suggests that UK can affect cell proliferation by cell cycle inhibition, showing a cell cycle G2/M arrest in UK-treated cells. Conclusion: Our results suggest that UK modulates two major aspects involved in tumorigenesis of pancreatic cancer cells, such as extracellular matrix remodeling and cell proliferation.

Original languageEnglish
Pages (from-to)545-552
Number of pages8
JournalPancreatology
Volume10
Issue number5
DOIs
Publication statusPublished - Dec 2010

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ukrain
Matrix Metalloproteinase 9
Pancreatic Neoplasms
Cysteine
Phenotype
Proteins
Matrix Metalloproteinase 2
Extracellular Matrix
Cell Cycle
Cell Proliferation
G2 Phase Cell Cycle Checkpoints
Messenger RNA
Tumor Microenvironment
In Vitro Techniques
Therapeutic Uses
Tumor Biomarkers
Real-Time Polymerase Chain Reaction
Carcinogenesis

Keywords

  • Matrix metalloproteinases
  • Pancreatic ductal adenocarcinoma
  • Secreted protein acidic and rich in cysteine
  • Tumor invasion

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Hepatology

Cite this

Funel, N., Costa, F., Pettinari, L., Taddeo, A., Sala, A., Chiriva-Internati, M., ... Gagliano, N. (2010). Ukrain affects pancreas cancer cell phenotype in vitro by targeting MMP-9 and intra-/extracellular SPARC expression. Pancreatology, 10(5), 545-552. https://doi.org/10.1159/000266127

Ukrain affects pancreas cancer cell phenotype in vitro by targeting MMP-9 and intra-/extracellular SPARC expression. / Funel, Niccola; Costa, Francesco; Pettinari, Letizia; Taddeo, Adriano; Sala, Alessandra; Chiriva-Internati, Maurizio; Cobos, Everardo; Colombo, Graziano; Milzani, Aldo; Campani, Daniela; Dalle-Donne, Isabella; Gagliano, Nicoletta.

In: Pancreatology, Vol. 10, No. 5, 12.2010, p. 545-552.

Research output: Contribution to journalArticle

Funel, N, Costa, F, Pettinari, L, Taddeo, A, Sala, A, Chiriva-Internati, M, Cobos, E, Colombo, G, Milzani, A, Campani, D, Dalle-Donne, I & Gagliano, N 2010, 'Ukrain affects pancreas cancer cell phenotype in vitro by targeting MMP-9 and intra-/extracellular SPARC expression', Pancreatology, vol. 10, no. 5, pp. 545-552. https://doi.org/10.1159/000266127
Funel, Niccola ; Costa, Francesco ; Pettinari, Letizia ; Taddeo, Adriano ; Sala, Alessandra ; Chiriva-Internati, Maurizio ; Cobos, Everardo ; Colombo, Graziano ; Milzani, Aldo ; Campani, Daniela ; Dalle-Donne, Isabella ; Gagliano, Nicoletta. / Ukrain affects pancreas cancer cell phenotype in vitro by targeting MMP-9 and intra-/extracellular SPARC expression. In: Pancreatology. 2010 ; Vol. 10, No. 5. pp. 545-552.
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abstract = "Background/Aims: We investigated whether the anticancer drug Ukrain (UK) is able to modulate the expression of some of the key markers of tumor progression in pancreatic cell carcinoma, in order to assess its potential therapeutic effect. Methods: Three cell lines (HPAF-II, PL45, HPAC) were treated with UK (5, 10 and 20 μM) for 48 h, or left untreated. Secreted protein acidic and rich in cysteine (SPARC) mRNA levels were assessed by real-time PCR. Matrix metalloproteinases (MMP)-2 and -9 activity was analyzed by SDS zymography; SPARC protein levels in cell lysates and supernatants were determined by Western blot. Cell cycle was determined by flow cytometric analysis, and invasion by matrigel invasion assay. Results: UK down-regulated MMP-2 and MMP-9, suggesting that UK may decrease pancreatic cancer cell invasion, as confirmed by the matrigel invasion assay. SPARC protein down-regulation in supernatants points to an inhibition by UK of extracellular matrix remodeling in the tumor microenvironment. At the same time, SPARC mRNA and cellular protein level up-regulation suggests that UK can affect cell proliferation by cell cycle inhibition, showing a cell cycle G2/M arrest in UK-treated cells. Conclusion: Our results suggest that UK modulates two major aspects involved in tumorigenesis of pancreatic cancer cells, such as extracellular matrix remodeling and cell proliferation.",
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