Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell lines

IGFBP-6 inhibits angiogenesis as well as proliferation and survival of rhabdomyosarcoma cells. However, it promotes migration of these cells in an IGF-independent manner. The IGF system is implicated in ovarian cancer, so we studied the effects of IGFBP-6 in ovarian cancer cells.Methods: The effects...

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Main Authors: Zhiyong eYang, Leon A Bach
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-01-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fendo.2014.00231/full
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author Zhiyong eYang
Leon A Bach
Leon A Bach
author_facet Zhiyong eYang
Leon A Bach
Leon A Bach
author_sort Zhiyong eYang
collection DOAJ
description IGFBP-6 inhibits angiogenesis as well as proliferation and survival of rhabdomyosarcoma cells. However, it promotes migration of these cells in an IGF-independent manner. The IGF system is implicated in ovarian cancer, so we studied the effects of IGFBP-6 in ovarian cancer cells.Methods: The effects of wild type (wt) and a non-IGF-binding mutant (m) of IGFBP-6 on migration of HEY and SKOV-3 ovarian cancer cells, which respectively represent aggressive and transitional cancers, were studied. ERK and JNK phosphorylation were measured by Western blotting.Results: IGF-II, wt- and mIGFBP-6 each promoted SKOV3 cell migration by 77-98% (p<0.01). In contrast, IGF-II also increased HEY cell migration to 155 ± 13% of control (p<0.001), but wtIGFBP-6 and mIGFBP-6 decreased migration to 62 ± 5% and 66 ± 3% respectively (p<0.001). In these cells, coincubation of IGF-II with wt but not mIGFBP-6 increased migration. MAP kinase pathways are involved in IGFBP-6-induced rhabdomyosarcoma cell migration, so activation of these pathways in HEY and SKOV3 cells was studied. wt and mIGFBP-6 increased ERK phosphorylation by 62-99% in both cell lines (p<0.05). wtIGFBP-6 also increased JNK phosphorylation by 139-153% in both cell lines (p<0.05), but the effect of mIGFBP-6 was less clear. ERK and JNK inhibitors partially inhibited the migratory effects of wt and mIGFBP-6 in SKOV3 cells, whereas the ERK inhibitor partially restored wt and mIGFBP-6-induced inhibition of HEY cell migration. The JNK inhibitor had a lesser effect on the actions of wtIGFBP-6 and no effect on the actions of mIGFBP-6 in HEY cells.Conclusions: IGFBP-6 has opposing effects on migration of HEY and SKOV3 ovarian cancer cells, but activates MAP kinase pathways in both. Delineating the pathways underlying the differential effects on migration will increase our understanding of ovarian cancer metastasis and shed new light on the IGF-independent effects of IGFBP-6.
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spelling doaj.art-170c1d0bdad74b74ba2252cdee03ea8e2022-12-21T17:33:33ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922015-01-01510.3389/fendo.2014.00231124177Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell linesZhiyong eYang0Leon A Bach1Leon A Bach2Monash UniversityMonash UniversityAlfred HospitalIGFBP-6 inhibits angiogenesis as well as proliferation and survival of rhabdomyosarcoma cells. However, it promotes migration of these cells in an IGF-independent manner. The IGF system is implicated in ovarian cancer, so we studied the effects of IGFBP-6 in ovarian cancer cells.Methods: The effects of wild type (wt) and a non-IGF-binding mutant (m) of IGFBP-6 on migration of HEY and SKOV-3 ovarian cancer cells, which respectively represent aggressive and transitional cancers, were studied. ERK and JNK phosphorylation were measured by Western blotting.Results: IGF-II, wt- and mIGFBP-6 each promoted SKOV3 cell migration by 77-98% (p<0.01). In contrast, IGF-II also increased HEY cell migration to 155 ± 13% of control (p<0.001), but wtIGFBP-6 and mIGFBP-6 decreased migration to 62 ± 5% and 66 ± 3% respectively (p<0.001). In these cells, coincubation of IGF-II with wt but not mIGFBP-6 increased migration. MAP kinase pathways are involved in IGFBP-6-induced rhabdomyosarcoma cell migration, so activation of these pathways in HEY and SKOV3 cells was studied. wt and mIGFBP-6 increased ERK phosphorylation by 62-99% in both cell lines (p<0.05). wtIGFBP-6 also increased JNK phosphorylation by 139-153% in both cell lines (p<0.05), but the effect of mIGFBP-6 was less clear. ERK and JNK inhibitors partially inhibited the migratory effects of wt and mIGFBP-6 in SKOV3 cells, whereas the ERK inhibitor partially restored wt and mIGFBP-6-induced inhibition of HEY cell migration. The JNK inhibitor had a lesser effect on the actions of wtIGFBP-6 and no effect on the actions of mIGFBP-6 in HEY cells.Conclusions: IGFBP-6 has opposing effects on migration of HEY and SKOV3 ovarian cancer cells, but activates MAP kinase pathways in both. Delineating the pathways underlying the differential effects on migration will increase our understanding of ovarian cancer metastasis and shed new light on the IGF-independent effects of IGFBP-6.http://journal.frontiersin.org/Journal/10.3389/fendo.2014.00231/fullMigrationovarian cancerInsulin-like growth factorMAP kinaseInsulin-like growth factor binding protein-6
spellingShingle Zhiyong eYang
Leon A Bach
Leon A Bach
Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell lines
Frontiers in Endocrinology
Migration
ovarian cancer
Insulin-like growth factor
MAP kinase
Insulin-like growth factor binding protein-6
title Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell lines
title_full Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell lines
title_fullStr Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell lines
title_full_unstemmed Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell lines
title_short Differential effects of insulin-like growth factor binding protein-6 (IGFBP-6) on migration of two ovarian cancer cell lines
title_sort differential effects of insulin like growth factor binding protein 6 igfbp 6 on migration of two ovarian cancer cell lines
topic Migration
ovarian cancer
Insulin-like growth factor
MAP kinase
Insulin-like growth factor binding protein-6
url http://journal.frontiersin.org/Journal/10.3389/fendo.2014.00231/full
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