Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy

Ghassan Ayish Alyahya; Miriam Kolko; Jan Ulrik Prause; Boye Schnack Nielsen; Jinmei Wang; Steffen Heegaard; Miriam Kolko

doi:10.1167/iovs.07-1436

Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy

Ghassan Ayish Alyahya, Miriam Kolko, Jan Ulrik Prause, Boye Schnack Nielsen, Jinmei Wang, Steffen Heegaard, Miriam Kolko

6 Citations (Scopus)

Abstract

PURPOSE: To correlate the expression of matrix metalloproteinases (MMPs) with melanoma-associated spongiform scleropathy (MASS) and scleral tumor invasion in eyes with uveal melanoma.

METHODS: Eleven specimens with MASS and 11 eyes without MASS were investigated. Sections were examined for MMP-1, -2, -9, and -13 mRNA expression by in situ hybridization with (35)S-radiolabeled riboprobes. Immunohistochemical studies of the same specimens were conducted with MMP-2-specific antibodies. For double-labeling experiments, primary MMP-2-specific antibodies and antibodies binding to fibroblasts and macrophages were used.

RESULTS: MMP-2 mRNA expression was detected in 10 (91%) of 11 eyes with MASS and scleral tumor invasion. In eight (73%) of these cases, the expression signals were seen in numerous scleral fibroblasts. In melanoma cases without MASS, MMP-2 mRNA expression was detected in four (36%) cases, and only one (9%) showed numerous positive cells. Tumor-infiltrating macrophages were found to harbor MMP-2, shown by a double-labeling experiment. The MMP-2 expression by immunostaining coincides with MMP-2 expression by in situ hybridization. No MMP-2 expression was detected in the tumor cells.

CONCLUSIONS: MASS is considered a tumor-induced scleral degradation process. There is a significantly higher expression of MMP-2 in MASS-positive areas, indicating that MMP-2 is involved in the development of MASS and that MMP-2 is produced by scleral fibroblasts under the influence of tumor cells and/or tumor-infiltrating macrophages. These changes may represent a step in the invasion of uveal melanoma by facilitating the spread of tumor cells through the sclera.

Original language	English
Journal	Investigative Ophthalmology & Visual Science
Volume	49
Issue number	7
Pages (from-to)	2806-11
Number of pages	6
ISSN	0146-0404
DOIs	https://doi.org/10.1167/iovs.07-1436
Publication status	Published - Jul 2008

Keywords

Choroid Neoplasms
Fibroblasts
Humans
Immunohistochemistry
In Situ Hybridization
Macrophages
Matrix Metalloproteinase 2
Melanoma
Neoplasm Invasiveness
RNA, Messenger
Sclera
Scleral Diseases
Staining and Labeling
Up-Regulation

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10.1167/iovs.07-1436

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@article{7bd787c983374d278773925394c7a857,

title = "Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy",

abstract = "PURPOSE: To correlate the expression of matrix metalloproteinases (MMPs) with melanoma-associated spongiform scleropathy (MASS) and scleral tumor invasion in eyes with uveal melanoma.METHODS: Eleven specimens with MASS and 11 eyes without MASS were investigated. Sections were examined for MMP-1, -2, -9, and -13 mRNA expression by in situ hybridization with (35)S-radiolabeled riboprobes. Immunohistochemical studies of the same specimens were conducted with MMP-2-specific antibodies. For double-labeling experiments, primary MMP-2-specific antibodies and antibodies binding to fibroblasts and macrophages were used.RESULTS: MMP-2 mRNA expression was detected in 10 (91%) of 11 eyes with MASS and scleral tumor invasion. In eight (73%) of these cases, the expression signals were seen in numerous scleral fibroblasts. In melanoma cases without MASS, MMP-2 mRNA expression was detected in four (36%) cases, and only one (9%) showed numerous positive cells. Tumor-infiltrating macrophages were found to harbor MMP-2, shown by a double-labeling experiment. The MMP-2 expression by immunostaining coincides with MMP-2 expression by in situ hybridization. No MMP-2 expression was detected in the tumor cells.CONCLUSIONS: MASS is considered a tumor-induced scleral degradation process. There is a significantly higher expression of MMP-2 in MASS-positive areas, indicating that MMP-2 is involved in the development of MASS and that MMP-2 is produced by scleral fibroblasts under the influence of tumor cells and/or tumor-infiltrating macrophages. These changes may represent a step in the invasion of uveal melanoma by facilitating the spread of tumor cells through the sclera.",

keywords = "Choroid Neoplasms, Fibroblasts, Humans, Immunohistochemistry, In Situ Hybridization, Macrophages, Matrix Metalloproteinase 2, Melanoma, Neoplasm Invasiveness, RNA, Messenger, Sclera, Scleral Diseases, Staining and Labeling, Up-Regulation",

author = "Alyahya, {Ghassan Ayish} and Miriam Kolko and Prause, {Jan Ulrik} and Nielsen, {Boye Schnack} and Jinmei Wang and Steffen Heegaard and Miriam Kolko",

year = "2008",

month = jul,

doi = "10.1167/iovs.07-1436",

language = "English",

volume = "49",

pages = "2806--11",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

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

number = "7",

}

TY - JOUR

T1 - Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy

AU - Alyahya, Ghassan Ayish

AU - Kolko, Miriam

AU - Prause, Jan Ulrik

AU - Nielsen, Boye Schnack

AU - Wang, Jinmei

AU - Heegaard, Steffen

AU - Kolko, Miriam

PY - 2008/7

Y1 - 2008/7

N2 - PURPOSE: To correlate the expression of matrix metalloproteinases (MMPs) with melanoma-associated spongiform scleropathy (MASS) and scleral tumor invasion in eyes with uveal melanoma.METHODS: Eleven specimens with MASS and 11 eyes without MASS were investigated. Sections were examined for MMP-1, -2, -9, and -13 mRNA expression by in situ hybridization with (35)S-radiolabeled riboprobes. Immunohistochemical studies of the same specimens were conducted with MMP-2-specific antibodies. For double-labeling experiments, primary MMP-2-specific antibodies and antibodies binding to fibroblasts and macrophages were used.RESULTS: MMP-2 mRNA expression was detected in 10 (91%) of 11 eyes with MASS and scleral tumor invasion. In eight (73%) of these cases, the expression signals were seen in numerous scleral fibroblasts. In melanoma cases without MASS, MMP-2 mRNA expression was detected in four (36%) cases, and only one (9%) showed numerous positive cells. Tumor-infiltrating macrophages were found to harbor MMP-2, shown by a double-labeling experiment. The MMP-2 expression by immunostaining coincides with MMP-2 expression by in situ hybridization. No MMP-2 expression was detected in the tumor cells.CONCLUSIONS: MASS is considered a tumor-induced scleral degradation process. There is a significantly higher expression of MMP-2 in MASS-positive areas, indicating that MMP-2 is involved in the development of MASS and that MMP-2 is produced by scleral fibroblasts under the influence of tumor cells and/or tumor-infiltrating macrophages. These changes may represent a step in the invasion of uveal melanoma by facilitating the spread of tumor cells through the sclera.

AB - PURPOSE: To correlate the expression of matrix metalloproteinases (MMPs) with melanoma-associated spongiform scleropathy (MASS) and scleral tumor invasion in eyes with uveal melanoma.METHODS: Eleven specimens with MASS and 11 eyes without MASS were investigated. Sections were examined for MMP-1, -2, -9, and -13 mRNA expression by in situ hybridization with (35)S-radiolabeled riboprobes. Immunohistochemical studies of the same specimens were conducted with MMP-2-specific antibodies. For double-labeling experiments, primary MMP-2-specific antibodies and antibodies binding to fibroblasts and macrophages were used.RESULTS: MMP-2 mRNA expression was detected in 10 (91%) of 11 eyes with MASS and scleral tumor invasion. In eight (73%) of these cases, the expression signals were seen in numerous scleral fibroblasts. In melanoma cases without MASS, MMP-2 mRNA expression was detected in four (36%) cases, and only one (9%) showed numerous positive cells. Tumor-infiltrating macrophages were found to harbor MMP-2, shown by a double-labeling experiment. The MMP-2 expression by immunostaining coincides with MMP-2 expression by in situ hybridization. No MMP-2 expression was detected in the tumor cells.CONCLUSIONS: MASS is considered a tumor-induced scleral degradation process. There is a significantly higher expression of MMP-2 in MASS-positive areas, indicating that MMP-2 is involved in the development of MASS and that MMP-2 is produced by scleral fibroblasts under the influence of tumor cells and/or tumor-infiltrating macrophages. These changes may represent a step in the invasion of uveal melanoma by facilitating the spread of tumor cells through the sclera.

KW - Choroid Neoplasms

KW - Fibroblasts

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Macrophages

KW - Matrix Metalloproteinase 2

KW - Melanoma

KW - Neoplasm Invasiveness

KW - RNA, Messenger

KW - Sclera

KW - Scleral Diseases

KW - Staining and Labeling

KW - Up-Regulation

U2 - 10.1167/iovs.07-1436

DO - 10.1167/iovs.07-1436

M3 - Journal article

C2 - 18579756

SN - 0146-0404

VL - 49

SP - 2806

EP - 2811

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 7

ER -

Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy

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Keywords

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