Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo

Nick Devoogdt, Nabila Rasool, Ebony Hoskins, Fiona Simpkins, Nana Tchabo, Elise C. Kohn

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions (P ≤ 0.02), in soft agar colony number and size (P ≤ 0.05), and in anoikis resistance (P ≤ 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining (P ≤ 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination.

Original languageEnglish (US)
Pages (from-to)434-440
Number of pages7
JournalCancer Science
Volume100
Issue number3
DOIs
StatePublished - Apr 30 2009
Externally publishedYes

Fingerprint

Secretory Leukocyte Peptidase Inhibitor
Protease Inhibitors
Ovarian Neoplasms
Heterografts
In Vitro Techniques
Anoikis
Leukocyte Elastase
Enzyme Assays
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Devoogdt, Nick ; Rasool, Nabila ; Hoskins, Ebony ; Simpkins, Fiona ; Tchabo, Nana ; Kohn, Elise C. / Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo. In: Cancer Science. 2009 ; Vol. 100, No. 3. pp. 434-440.
@article{341c723107c84e47a1472da9e2895bf3,
title = "Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo",
abstract = "The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions (P ≤ 0.02), in soft agar colony number and size (P ≤ 0.05), and in anoikis resistance (P ≤ 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining (P ≤ 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination.",
author = "Nick Devoogdt and Nabila Rasool and Ebony Hoskins and Fiona Simpkins and Nana Tchabo and Kohn, {Elise C.}",
year = "2009",
month = "4",
day = "30",
doi = "10.1111/j.1349-7006.2009.01076.x",
language = "English (US)",
volume = "100",
pages = "434--440",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "3",

}

Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo. / Devoogdt, Nick; Rasool, Nabila; Hoskins, Ebony; Simpkins, Fiona; Tchabo, Nana; Kohn, Elise C.

In: Cancer Science, Vol. 100, No. 3, 30.04.2009, p. 434-440.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overexpression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo

AU - Devoogdt, Nick

AU - Rasool, Nabila

AU - Hoskins, Ebony

AU - Simpkins, Fiona

AU - Tchabo, Nana

AU - Kohn, Elise C.

PY - 2009/4/30

Y1 - 2009/4/30

N2 - The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions (P ≤ 0.02), in soft agar colony number and size (P ≤ 0.05), and in anoikis resistance (P ≤ 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining (P ≤ 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination.

AB - The alarm anti-protease secretory leukocyte protease inhibitor (SLPI) is frequently overexpressed in ovarian cancer cells and has been proposed for inclusion in biomarker panels but function remains unclear. We hypothesized that SLPI overexpression promotes ovarian cancer growth and survival. Low SLPI-expressing Hey-A8 ovarian cancer cells were engineered to produce functional (WT) or protease inhibitor-null (PI-) mutant SLPI; lack of PI activity was confirmed by enzymatic assay. WT/SLPI and PI- mutants stimulated significant proliferation and survival of Hey-A8 ovarian cancer cells under basal culture conditions (P ≤ 0.02), in soft agar colony number and size (P ≤ 0.05), and in anoikis resistance (P ≤ 0.005). SLPI protected the ovarian cancer survival factor, progranulin (PRGN), and HEY-A8 cells from degradation and apoptosis due to neutrophil elastase. PI-/SLPI cells had greater protective activity than WT/SLPI cells. HEY-A8 murine xenografts revealed enhanced solid tumor formation, dissemination, and invasion in WT/SLPI and PI-/SLPI mutants. Increased proliferation was demonstrated by Ki-67 staining (P ≤ 0.02). Increased secreted PRGN was seen in culture and was also observed by immunohistochemistry in the SLPI transfectant xenografts. This study describes a PI-independent function for SLPI in ovarian cancer growth and dissemination.

UR - http://www.scopus.com/inward/record.url?scp=62849105134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62849105134&partnerID=8YFLogxK

U2 - 10.1111/j.1349-7006.2009.01076.x

DO - 10.1111/j.1349-7006.2009.01076.x

M3 - Article

VL - 100

SP - 434

EP - 440

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 3

ER -