Author of

• 10525

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  P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10540

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    P1.02-015 - Diverse effects of PAI-1 proteins on lung and prostate cancer cell invasion. (ID 2717)

    09:30 - 16:30  |  Author(s): A. Rozy
    • Abstract

    Background
    Acquisition of ability to uncontrolled migration is one of the fundamental properties of cancer cells, enabling them to infiltrate tissues and metastasize. PAI-1 is the major physiological inhibitor of urokinase (uPA), which plays a key role in migration and invasion of tumor cells.

    Methods
    The aim of present study was to analyze the impact of increasing concentrations of PAI-1 mutated forms: VLHL PAI-1 with very long half-life time, Vn neg PAI-1 - devoid of affinity towards vitronectin and wPAI -1 on lung (A549, NCI-H1299) and prostate (LNCaP, DU145) cancer cells invasive activity. Selected cell lines are characterized by different (normal and high) urokinase production.

    Results
    No effect of PAI-1 proteins on invasiveness of lung cancer cells was observed, while dose-dependent significant inhibition was demonstrated in both prostate cancer lines (DU145 and LNCaP) cultured with VLHL PAI-1 (respectively p<0,05 and p<0,01) and Vn PAI-1 neg (p<0,05). Not surprisingly wPAI-1 significantly stimulated prostate cancer cells invasiveness in all concentrations.

    Conclusion
    PAI-1 inhibitory effect on prostate cancer invasive activity is associated with anti-proteinase activity. Lung cancer cells invasiveness regulation seems not to be PAI-1-urokinase regulated.

• 12386

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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12402

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    P3.02-016 - Proteinase inhibition regulates the anti-tumor activity of PAI-1 towards lung and prostate cancer cells (ID 2706)

    09:30 - 16:30  |  Author(s): A. Rozy
    • Abstract

    Background
    Plasminogen activator inhibitor type 1 (PAI-1) plays an important role in tumor growth and metastasis formation, directly via specific urokinase complexing or indirectly due to its affinity to vitronectin.

    Methods
    The aim of this study was to analyze the impact of the mutant forms of PAI-1: very long half-life (VLHL PAI-1) or devoid of affinity towards vitronectin (Vn neg PAI-1) and wild form (wPAI -1) on proliferation of lung cancer (A549 and H1299 ) and prostate cancer (LNCaP and DU145) cells characterized by different proteinase (urokinase) production.

    Results
    The dose- and time-dependent inhibition of cell proliferation in the presence of VLHL PAI-1 was evident in A549 and LNCaP cultures. In H1299 cells inhibitory effect was only dose-depended (p<0.001), while in DU145 only 100 mg/ml of VLHL PAI-1 in 72 hrs cultures suppresed prostate cancer cells proliferative activity (p <0.001). No significant effect of Vn neg PAI-1 on the proliferation of A549 and H1299 was observed while in prostate cancer lines (DU145, LNCaP) only the inhibitory effect of the highest Vn neg PAI-1 concentration (100μg/ml) was evident (p <0.001) but not time-dependent. wPAI-1 did’t affect A549 and LNCaP proliferation while in highest concentration it had the stimulating effect on H1299 and Du145 (24,48 hrs cultures).

    Conclusion
    PAI-1 is a negative regulator of cancer cells proliferation due to its anti-proteinase activity. Its biological effect on lung cancer cells is time and dose-dependent.