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Published in: Tumor Biology 8/2015

01-08-2015 | Research Article

Effect of cancer-associated fibroblasts on the migration of glioma cells in vitro

Authors: Jana Trylcova, Petr Busek, Karel Smetana Jr., Eva Balaziova, Barbora Dvorankova, Alzbeta Mifkova, Aleksi Sedo

Published in: Tumor Biology | Issue 8/2015

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Abstract

Cancer-associated fibroblasts (CAFs) significantly influence biological properties of many tumors. The role of these mesenchymal cells is also anticipated in human gliomas. To evaluate the putative role of CAFs in glioblastoma, we tested the effect of CAF conditioned media on the proliferation and chemotaxis of glioma cells. The proliferation of glioma cells was stimulated to similar extent by both the normal fibroblasts (NFs) and CAF-conditioned media. Nevertheless, CAF-conditioned media enhanced the chemotactic migration of glioma cells significantly more potently than the media from normal fibroblasts. In order to determine whether CAF-like cells are present in human glioblastomas, immunofluorescence staining was performed on tissue samples from 20 patients using markers typical for CAFs. This analysis revealed regular presence of mesenchymal cells expressing characteristic CAF markers α-smooth muscle actin and TE-7 in human glioblastomas. These observations indicate the potential role of CAF-like cells in glioblastoma biology.
Literature
2.
3.
go back to reference Goodpaster T, Legesse-Miller A, Hameed MR, Aisner SC, Randolph-Habecker J, Coller HA. An immunohistochemical method for identifying fibroblasts in formalin-fixed, paraffin-embedded tissue. J Histochem Cytochem Off J Histochem Soc. 2008;56(4):347–58. doi:10.1369/jhc.7A7287.2007.CrossRef Goodpaster T, Legesse-Miller A, Hameed MR, Aisner SC, Randolph-Habecker J, Coller HA. An immunohistochemical method for identifying fibroblasts in formalin-fixed, paraffin-embedded tissue. J Histochem Cytochem Off J Histochem Soc. 2008;56(4):347–58. doi:10.​1369/​jhc.​7A7287.​2007.CrossRef
4.
go back to reference Smetana K, Dvorankova B, Szabo P, Strnad H, Kolar M. Role of stromal fibroblasts in cancer originated from squamous epithelia. In: Bai X, editor. Dermal fibroblasts: histological perspectives, characterization and role in disease. New York: Nova Sciences Publishers; 2013. p. 83–94. Smetana K, Dvorankova B, Szabo P, Strnad H, Kolar M. Role of stromal fibroblasts in cancer originated from squamous epithelia. In: Bai X, editor. Dermal fibroblasts: histological perspectives, characterization and role in disease. New York: Nova Sciences Publishers; 2013. p. 83–94.
5.
go back to reference De Wever O, Demetter P, Mareel M, Bracke M. Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer J Int du Cancer. 2008;123(10):2229–38. doi:10.1002/ijc.23925.CrossRef De Wever O, Demetter P, Mareel M, Bracke M. Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer J Int du Cancer. 2008;123(10):2229–38. doi:10.​1002/​ijc.​23925.CrossRef
6.
go back to reference Haviv I, Polyak K, Qiu W, Hu M, Campbell I. Origin of carcinoma associated fibroblasts. Cell Cycle. 2009;8(4):589–95.CrossRefPubMed Haviv I, Polyak K, Qiu W, Hu M, Campbell I. Origin of carcinoma associated fibroblasts. Cell Cycle. 2009;8(4):589–95.CrossRefPubMed
7.
go back to reference Strnad H, Lacina L, Kolar M, Cada Z, Vlcek C, Dvorankova B, et al. Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes. Histochem Cell Biol. 2010;133(2):201–11. doi:10.1007/s00418-009-0661-6.CrossRefPubMed Strnad H, Lacina L, Kolar M, Cada Z, Vlcek C, Dvorankova B, et al. Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes. Histochem Cell Biol. 2010;133(2):201–11. doi:10.​1007/​s00418-009-0661-6.CrossRefPubMed
8.
go back to reference Kolar M, Szabo P, Dvorankova B, Lacina L, Gabius HJ, Strnad H, et al. Upregulation of IL-6, IL-8 and CXCL-1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: immunohistochemical and transcriptomic analyses. Biol Cell / Under Auspices Europ Cell Biol Org. 2012;104(12):738–51. doi:10.1111/boc.201200018. Kolar M, Szabo P, Dvorankova B, Lacina L, Gabius HJ, Strnad H, et al. Upregulation of IL-6, IL-8 and CXCL-1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: immunohistochemical and transcriptomic analyses. Biol Cell / Under Auspices Europ Cell Biol Org. 2012;104(12):738–51. doi:10.​1111/​boc.​201200018.
9.
go back to reference Dvorankova B, Szabo P, Lacina L, Gal P, Uhrova J, Zima T, et al. Human galectins induce conversion of dermal fibroblasts into myofibroblasts and production of extracellular matrix: potential application in tissue engineering and wound repair. Cells Tissues Organs. 2011;194(6):469–80. doi:10.1159/000324864.CrossRefPubMed Dvorankova B, Szabo P, Lacina L, Gal P, Uhrova J, Zima T, et al. Human galectins induce conversion of dermal fibroblasts into myofibroblasts and production of extracellular matrix: potential application in tissue engineering and wound repair. Cells Tissues Organs. 2011;194(6):469–80. doi:10.​1159/​000324864.CrossRefPubMed
10.
go back to reference Valach J, Fik Z, Strnad H, Chovanec M, Plzak J, Cada Z, et al. Smooth muscle actin-expressing stromal fibroblasts in head and neck squamous cell carcinoma: increased expression of galectin-1 and induction of poor prognosis factors. Int J Cancer J Int du Cancer. 2012;131(11):2499–508. doi:10.1002/ijc.27550.CrossRef Valach J, Fik Z, Strnad H, Chovanec M, Plzak J, Cada Z, et al. Smooth muscle actin-expressing stromal fibroblasts in head and neck squamous cell carcinoma: increased expression of galectin-1 and induction of poor prognosis factors. Int J Cancer J Int du Cancer. 2012;131(11):2499–508. doi:10.​1002/​ijc.​27550.CrossRef
11.
go back to reference Mifkova A, Kodet O, Szabo P, Kucera J, Dvorankova B, Andre S, et al. Synthetic polyamine BPA-C8 inhibits TGF-beta1-mediated conversion of human dermal fibroblast to myofibroblasts and establishment of galectin-1-rich extracellular matrix in vitro. Chembiochem Europ J Chem Biol. 2014;15(10):1465–70. doi:10.1002/cbic.201402087.CrossRef Mifkova A, Kodet O, Szabo P, Kucera J, Dvorankova B, Andre S, et al. Synthetic polyamine BPA-C8 inhibits TGF-beta1-mediated conversion of human dermal fibroblast to myofibroblasts and establishment of galectin-1-rich extracellular matrix in vitro. Chembiochem Europ J Chem Biol. 2014;15(10):1465–70. doi:10.​1002/​cbic.​201402087.CrossRef
12.
go back to reference Dvorankova B, Szabo P, Lacina L, Kodet O, Matouskova E, Smetana Jr K. Fibroblasts prepared from different types of malignant tumors stimulate expression of luminal marker keratin 8 in the EM-G3 breast cancer cell line. Histochem Cell Biol. 2012;137(5):679–85. doi:10.1007/s00418-012-0918-3.CrossRefPubMed Dvorankova B, Szabo P, Lacina L, Kodet O, Matouskova E, Smetana Jr K. Fibroblasts prepared from different types of malignant tumors stimulate expression of luminal marker keratin 8 in the EM-G3 breast cancer cell line. Histochem Cell Biol. 2012;137(5):679–85. doi:10.​1007/​s00418-012-0918-3.CrossRefPubMed
13.
go back to reference da Fonseca AC, Badie B. Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies. Clinic Dev Immunol. 2013;2013:264124. doi:10.1155/2013/264124. da Fonseca AC, Badie B. Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies. Clinic Dev Immunol. 2013;2013:264124. doi:10.​1155/​2013/​264124.
14.
go back to reference Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H. The brain tumor microenvironment. Glia. 2012;60(3):502–14.CrossRefPubMed Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H. The brain tumor microenvironment. Glia. 2012;60(3):502–14.CrossRefPubMed
15.
go back to reference Clavreul A, Etcheverry A, Chassevent A, Quillien V, Avril T, Jourdan ML, et al. Isolation of a new cell population in the glioblastoma microenvironment. J Neuro-Oncol. 2012;106(3):493–504. doi:10.1007/s11060-011-0701-7.CrossRef Clavreul A, Etcheverry A, Chassevent A, Quillien V, Avril T, Jourdan ML, et al. Isolation of a new cell population in the glioblastoma microenvironment. J Neuro-Oncol. 2012;106(3):493–504. doi:10.​1007/​s11060-011-0701-7.CrossRef
16.
go back to reference Clavreul A, Guette C, Faguer R, Tetaud C, Boissard A, Lemaire L, et al. Glioblastoma-associated stromal cells (GASCs) from histologically normal surgical margins have a myofibroblast phenotype and angiogenic properties. J Pathol. 2014;233(1):74–88. doi:10.1002/path.4332.CrossRefPubMed Clavreul A, Guette C, Faguer R, Tetaud C, Boissard A, Lemaire L, et al. Glioblastoma-associated stromal cells (GASCs) from histologically normal surgical margins have a myofibroblast phenotype and angiogenic properties. J Pathol. 2014;233(1):74–88. doi:10.​1002/​path.​4332.CrossRefPubMed
18.
go back to reference Haynes BF, Scearce RM, Lobach DF, Hensley LL. Phenotypic characterization and ontogeny of mesodermal-derived and endocrine epithelial components of the human thymic microenvironment. J Experiment Med. 1984;159(4):1149–68.CrossRef Haynes BF, Scearce RM, Lobach DF, Hensley LL. Phenotypic characterization and ontogeny of mesodermal-derived and endocrine epithelial components of the human thymic microenvironment. J Experiment Med. 1984;159(4):1149–68.CrossRef
23.
go back to reference Wesseling P, Schlingemann RO, Rietveld FJ, Link M, Burger PC, Ruiter DJ. Early and extensive contribution of pericytes/vascular smooth muscle cells to microvascular proliferation in glioblastoma multiforme: an immuno-light and immuno-electron microscopic study. J Neuropathol Exp Neurol. 1995;54(3):304–10.CrossRefPubMed Wesseling P, Schlingemann RO, Rietveld FJ, Link M, Burger PC, Ruiter DJ. Early and extensive contribution of pericytes/vascular smooth muscle cells to microvascular proliferation in glioblastoma multiforme: an immuno-light and immuno-electron microscopic study. J Neuropathol Exp Neurol. 1995;54(3):304–10.CrossRefPubMed
25.
go back to reference Behnan J, Isakson P, Joel M, Cilio C, Langmoen IA, Vik-Mo EO, et al. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression. Stem Cells. 2014;32(5):1110–23. doi:10.1002/stem.1614.CrossRefPubMed Behnan J, Isakson P, Joel M, Cilio C, Langmoen IA, Vik-Mo EO, et al. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression. Stem Cells. 2014;32(5):1110–23. doi:10.​1002/​stem.​1614.CrossRefPubMed
26.
go back to reference Birnbaum T, Hildebrandt J, Nuebling G, Sostak P, Straube A. Glioblastoma-dependent differentiation and angiogenic potential of human mesenchymal stem cells in vitro. J Neuro-Oncol. 2011;105(1):57–65. doi:10.1007/s11060-011-0561-1.CrossRef Birnbaum T, Hildebrandt J, Nuebling G, Sostak P, Straube A. Glioblastoma-dependent differentiation and angiogenic potential of human mesenchymal stem cells in vitro. J Neuro-Oncol. 2011;105(1):57–65. doi:10.​1007/​s11060-011-0561-1.CrossRef
27.
go back to reference Cornil I, Theodorescu D, Man S, Herlyn M, Jambrosic J, Kerbel RS. Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc Natl Acad Sci U S A. 1991;88(14):6028–32.CrossRefPubMedPubMedCentral Cornil I, Theodorescu D, Man S, Herlyn M, Jambrosic J, Kerbel RS. Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc Natl Acad Sci U S A. 1991;88(14):6028–32.CrossRefPubMedPubMedCentral
28.
go back to reference Prowse AB, McQuade LR, Bryant KJ, Marcal H, Gray PP. Identification of potential pluripotency determinants for human embryonic stem cells following proteomic analysis of human and mouse fibroblast conditioned media. J Proteome Res. 2007;6(9):3796–807. doi:10.1021/pr0702262.CrossRefPubMed Prowse AB, McQuade LR, Bryant KJ, Marcal H, Gray PP. Identification of potential pluripotency determinants for human embryonic stem cells following proteomic analysis of human and mouse fibroblast conditioned media. J Proteome Res. 2007;6(9):3796–807. doi:10.​1021/​pr0702262.CrossRefPubMed
30.
go back to reference Camby I, Belot N, Lefranc F, Sadeghi N, de Launoit Y, Kaltner H, et al. Galectin-1 modulates human glioblastoma cell migration into the brain through modifications to the actin cytoskeleton and levels of expression of small GTPases. J Neuropathol Exp Neurol. 2002;61(7):585–96.CrossRefPubMed Camby I, Belot N, Lefranc F, Sadeghi N, de Launoit Y, Kaltner H, et al. Galectin-1 modulates human glioblastoma cell migration into the brain through modifications to the actin cytoskeleton and levels of expression of small GTPases. J Neuropathol Exp Neurol. 2002;61(7):585–96.CrossRefPubMed
Metadata
Title
Effect of cancer-associated fibroblasts on the migration of glioma cells in vitro
Authors
Jana Trylcova
Petr Busek
Karel Smetana Jr.
Eva Balaziova
Barbora Dvorankova
Alzbeta Mifkova
Aleksi Sedo
Publication date
01-08-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 8/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3259-8

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