Increased Insulin-like Growth Factor 1 Activity Can Rescue KLE Endometrial-like Cells from Apoptosis

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Insulin-like growth factor 1 (IGF-1) promotes KLE endometrial-like cell growth and protects them from adriamycin-induced apoptosis, suggesting it may support ectopic endometrial cell survival.

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The study investigated how insulin-like growth factor-1 (IGF-1) affects KLE endometrial-like cells in vitro, motivated by reports that endometriosis peritoneal fluid contains protease activity that hydrolyzes IGFBP-3 and increases local IGF-1 bioavailability. KLE cells were assessed for IGF-1–dependent proliferation and were challenged with the apoptosis-inducing agent adriamycin (100 nM) in the presence or absence of IGF-1 (50 ng/ml), with apoptosis measured using trypan blue exclusion and DNA fragmentation/flow cytometry. IGF-1 increased KLE cell growth in a dose-dependent manner and protected these cells from adriamycin-induced apoptosis. The paper does not explicitly state limitations beyond using an endometrial-like cell line and an in vitro adriamycin apoptosis model, and it does not directly test patient peritoneal fluid protease activity as a causal mechanism. Relevance to endometriosis: it directly frames its results around endometriosis peritoneal fluid protease activity that increases IGF-1 availability and proposes that this could support ectopic survival and growth of endometrial cells.

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Abstract

BACKGROUND: The peritoneal fluid (PF) of women with endometriosis contains protease(s) activity able to hydrolyze insulin-like growth factor-binding protein 3 (IGFBP-3), increasing the bioavailability of insulin-like growth factor-1 (IGF-1) locally. Therefore, we characterized the effects of IGF-1 on KLE endometrial-like cells in vitro. MATERIALS AND METHODS: The mitogenic effect of IGF-1 was assessed by the analysis of the DNA content and cell count. Apoptosis was triggered experimentally by the 48 hr exposure of KLE cells to 100 nM of adriamycin in the presence and absence of IGF-1 (50 ng/ml). Adriamycin apoptosis of KLE cells was determined by the number of dead KLE cells using trypan blue exclusion and by the DNA fragmentation on simple agarose gel and flow cytometry of propidium iodide and HOECHST 33342-stained KLE cells using an EPICS 753 pulse cytometer. RESULTS: IGF-1 stimulated the growth of KLE cells in a dose-dependent manner (optimal dose of 50 ng/ml) and protected KLE cells from adriamycin (100 nM)-induced apoptosis. CONCLUSIONS: These data suggest that IGF-1 is a survival factor for KLE cells. Conceivably, increased IGF-1 activity in the PF can optimize both the survival and ectopic growth of endometrial cells in the peritoneal cavity.
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Abstract

Background The peritoneal fluid (PF) of women with endometriosis contains protease(s) activity able to hydrolyze insulin-like growth factor-binding protein 3 (IGFBP-3), increasing the bioavailability of insulin-like growth factor-1 (IGF-1) locally. Therefore, we characterized the effects of IGF-1 on KLE endometrial-like cells in vitro.

Materials and methods

The mitogenic effect of IGF-1 was assessed by the analysis of the DNA content and cell count. Apoptosis was triggered experimentally by the 48 hr exposure of KLE cells to 100 nM of adriamycin in the presence and absence of IGF-1 (50 ng/ml). Adriamycin apoptosis of KLE cells was determined by the number of dead KLE cells using trypan blue exclusion and by the DNA fragmentation on simple agarose gel and flow cytometry of propidium iodide and HOECHST 33342-stained KLE cells using an EPICS 753 pulse cytometer.

Results

IGF-1 stimulated the growth of KLE cells in a dose-dependent manner (optimal dose of 50 ng/ml) and protected KLE cells from adriamycin (100 nM)-induced apoptosis.

Conclusions

These data suggest that IGF-1 is a survival factor for KLE cells. Conceivably, increased IGF-1 activity in the PF can optimize both the survival and ectopic growth of endometrial cells in the peritoneal cavity. Similar content being viewed by others

References

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Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Koutsilieris, M., Mastrogamvrakis, G., Lembessis, P. et al. Increased Insulin-like Growth Factor 1 Activity Can Rescue KLE Endometrial-like Cells from Apoptosis. Mol Med 7, 20–26 (2001). https://doi.org/10.1007/BF03401835 Accepted: Published: Issue date: DOI: https://doi.org/10.1007/BF03401835

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endometriosis

MeSH descriptors

Endometrium Endometrium Insulin-Like Growth Factor I Apoptosis Apoptosis Apoptosis Ascitic Fluid Ascitic Fluid Cell Cycle Cell Cycle Cell Division Cell Division Cells, Cultured DNA Fragmentation Doxorubicin Doxorubicin Endometriosis Endometriosis Endometriosis Endometrium

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