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 language | English (US) |
|---|---|
| Pages (from-to) | 434-440 |
| Number of pages | 7 |
| Journal | Cancer Science |
| Volume | 100 |
| Issue number | 3 |
| DOIs | |
| State | Published - Apr 30 2009 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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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 journal › Article
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 -