Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis

Tina Jehs; Carsten Faber; Helene B Juel; Inge H G Bronkhorst; Martine J Jager; Mogens H Nissen

doi:10.1167/iovs.14-14394

Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis

Tina Jehs, Carsten Faber, Helene B Juel, Inge H G Bronkhorst, Martine J Jager, Mogens H Nissen

22 Citationer (Scopus)

Abstract

PURPOSE: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.

METHODS: We used an in vitro coculture system in which UM cell lines and T cells were cultured together, but separated by a membrane. Uveal melanoma gene expression was quantified using a microarray. Protein expression in the supernatant was quantified with ELISA or cytometric bead array. For the monocyte migration assay, a transwell plate was used.

RESULTS: Gene-expression analysis of UM cell lines showed that coculture with activated T cells resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1 (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines coincided with an increased chemotactic capacity of the supernatant toward monocytes.

CONCLUSIONS: Cytokines derived from activated T cells shifted the UM cell transcriptome toward a more inflammatory state, including upregulation of several chemokines, which led to an increased migration of monocytes. Therefore, UM cells might actively participate in generating a tumor-promoting inflammatory microenvironment.

Originalsprog	Engelsk
Tidsskrift	Investigative Ophthalmology & Visual Science
Vol/bind	55
Udgave nummer	8
Sider (fra-til)	5169-75
Antal sider	7
ISSN	0146-0404
DOI	https://doi.org/10.1167/iovs.14-14394
Status	Udgivet - 29 jul. 2014

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10.1167/iovs.14-14394

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@article{2115b030923b463ea9834d20d2a06aff,

title = "Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis",

abstract = "PURPOSE: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.METHODS: We used an in vitro coculture system in which UM cell lines and T cells were cultured together, but separated by a membrane. Uveal melanoma gene expression was quantified using a microarray. Protein expression in the supernatant was quantified with ELISA or cytometric bead array. For the monocyte migration assay, a transwell plate was used.RESULTS: Gene-expression analysis of UM cell lines showed that coculture with activated T cells resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1 (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines coincided with an increased chemotactic capacity of the supernatant toward monocytes.CONCLUSIONS: Cytokines derived from activated T cells shifted the UM cell transcriptome toward a more inflammatory state, including upregulation of several chemokines, which led to an increased migration of monocytes. Therefore, UM cells might actively participate in generating a tumor-promoting inflammatory microenvironment.",

keywords = "Cell Line, Tumor, Chemokines, Chemotaxis, Leukocyte, Coculture Techniques, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Humans, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating, Melanoma, Microarray Analysis, Monocytes, Uveal Neoplasms",

author = "Tina Jehs and Carsten Faber and Juel, {Helene B} and Bronkhorst, {Inge H G} and Jager, {Martine J} and Nissen, {Mogens H}",

year = "2014",

month = jul,

day = "29",

doi = "10.1167/iovs.14-14394",

language = "English",

volume = "55",

pages = "5169--75",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology",

number = "8",

}

TY - JOUR

T1 - Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis

AU - Jehs, Tina

AU - Faber, Carsten

AU - Juel, Helene B

AU - Bronkhorst, Inge H G

AU - Jager, Martine J

AU - Nissen, Mogens H

PY - 2014/7/29

Y1 - 2014/7/29

N2 - PURPOSE: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.METHODS: We used an in vitro coculture system in which UM cell lines and T cells were cultured together, but separated by a membrane. Uveal melanoma gene expression was quantified using a microarray. Protein expression in the supernatant was quantified with ELISA or cytometric bead array. For the monocyte migration assay, a transwell plate was used.RESULTS: Gene-expression analysis of UM cell lines showed that coculture with activated T cells resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1 (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines coincided with an increased chemotactic capacity of the supernatant toward monocytes.CONCLUSIONS: Cytokines derived from activated T cells shifted the UM cell transcriptome toward a more inflammatory state, including upregulation of several chemokines, which led to an increased migration of monocytes. Therefore, UM cells might actively participate in generating a tumor-promoting inflammatory microenvironment.

AB - PURPOSE: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.METHODS: We used an in vitro coculture system in which UM cell lines and T cells were cultured together, but separated by a membrane. Uveal melanoma gene expression was quantified using a microarray. Protein expression in the supernatant was quantified with ELISA or cytometric bead array. For the monocyte migration assay, a transwell plate was used.RESULTS: Gene-expression analysis of UM cell lines showed that coculture with activated T cells resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1 (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines coincided with an increased chemotactic capacity of the supernatant toward monocytes.CONCLUSIONS: Cytokines derived from activated T cells shifted the UM cell transcriptome toward a more inflammatory state, including upregulation of several chemokines, which led to an increased migration of monocytes. Therefore, UM cells might actively participate in generating a tumor-promoting inflammatory microenvironment.

KW - Cell Line, Tumor

KW - Chemokines

KW - Chemotaxis, Leukocyte

KW - Coculture Techniques

KW - Enzyme-Linked Immunosorbent Assay

KW - Gene Expression Regulation

KW - Humans

KW - Lymphocyte Activation

KW - Lymphocytes, Tumor-Infiltrating

KW - Melanoma

KW - Microarray Analysis

KW - Monocytes

KW - Uveal Neoplasms

U2 - 10.1167/iovs.14-14394

DO - 10.1167/iovs.14-14394

M3 - Journal article

C2 - 25074768

SN - 0146-0404

VL - 55

SP - 5169

EP - 5175

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 8

ER -

Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis

Abstract

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