Endothelin-1 in the tumor microenvironment correlates with melanoma invasion

Luis Chiriboga; Shane Meehan; Iman Osman; Michael Glick; Gelo de la Cruz; Brittny S Howell; George Friedman-Jiménez; Robert J Schneider; Sumayah Jamal

doi:10.1097/cmr.0000000000000235

Endothelin-1 in the tumor microenvironment correlates with melanoma invasion

Luis Chiriboga, Shane Meehan, Iman Osman, Michael Glick, Gelo de la Cruz, Brittny S Howell, George Friedman-Jiménez, Robert J Schneider, Sumayah Jamal

9 Citationer (Scopus)

Abstract

Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.

Originalsprog	Engelsk
Tidsskrift	Melanoma Research
Vol/bind	26
Udgave nummer	3
Sider (fra-til)	236-44
Antal sider	9
ISSN	0960-8931
DOI	https://doi.org/10.1097/cmr.0000000000000235
Status	Udgivet - jun. 2016
Udgivet eksternt	Ja

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10.1097/cmr.0000000000000235

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title = "Endothelin-1 in the tumor microenvironment correlates with melanoma invasion",

abstract = "Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.",

keywords = "Animals, Endothelin-1/metabolism, Humans, Immunohistochemistry, Melanoma/genetics, Neoplasm Invasiveness, Skin Neoplasms/metabolism, Tumor Microenvironment",

author = "Luis Chiriboga and Shane Meehan and Iman Osman and Michael Glick and {de la Cruz}, Gelo and Howell, {Brittny S} and George Friedman-Jim{\'e}nez and Schneider, {Robert J} and Sumayah Jamal",

year = "2016",

month = jun,

doi = "10.1097/cmr.0000000000000235",

language = "English",

volume = "26",

pages = "236--44",

journal = "Melanoma Research",

issn = "0960-8931",

publisher = "Lippincott Williams & Wilkins, Ltd.",

number = "3",

}

TY - JOUR

T1 - Endothelin-1 in the tumor microenvironment correlates with melanoma invasion

AU - Chiriboga, Luis

AU - Meehan, Shane

AU - Osman, Iman

AU - Glick, Michael

AU - de la Cruz, Gelo

AU - Howell, Brittny S

AU - Friedman-Jiménez, George

AU - Schneider, Robert J

AU - Jamal, Sumayah

PY - 2016/6

Y1 - 2016/6

N2 - Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.

AB - Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.

KW - Animals

KW - Endothelin-1/metabolism

KW - Humans

KW - Immunohistochemistry

KW - Melanoma/genetics

KW - Neoplasm Invasiveness

KW - Skin Neoplasms/metabolism

KW - Tumor Microenvironment

U2 - 10.1097/cmr.0000000000000235

DO - 10.1097/cmr.0000000000000235

M3 - Journal article

C2 - 26825037

SN - 0960-8931

VL - 26

SP - 236

EP - 244

JO - Melanoma Research

JF - Melanoma Research

IS - 3

ER -

Endothelin-1 in the tumor microenvironment correlates with melanoma invasion

Abstract

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