Regulation of Interleukin-8 Expression in Human Melanoma Cells by the Organ Environment

Mordechai Gutman, Rakesh K. Singh, Keping Xie, Corazon D. Bucana, Isaiah J. Fidler

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

The in vitro expression level of interleukin-8 (IL-8) correlates with the metastatic potential of human melanoma cells. The purpose of this study was to determine whether the expression level of IL-8 in human melanoma cells is influenced by the organ microenvironment A375P cells, a low metastatic human melanoma, and A375SM cells, a highly metastatic variant, were injected into the subcutis (s.c), spleen (to produce liver metastases), and lateral tail vein (to produce lung metastases) of athymic nude mice. Northern blot and immunohistochemical analyses determined that s.c. tumors, lung lesions, and liver lesions expressed high, intermediate, and low IL-8, mRNA, and protein, respectively. This differential regulation of IL-8 was not due to the size or density of the lesions or to selection of subpopulations of cells. We based this conclusion on the results of three experiments: (a) melanoma cell lines established in culture from in vivo-growing tumors exhibited similar levels of IL-8 mRNA transcripts; (b) in a crossover experiment, the level of IL-8 mRNA was always high in A375 tumors reestablished in the skin and low in the tumors reestablished in the liver, regardless of whether the melanoma cells had been first harvested from s.c. or liver tumors; and (c) A375 melanoma cells cocul-tured with human keratinocytes produced high levels of IL-8 protein, whereas A375 cells cocultured with highly differentiated human hepatoma cells produced decreased levels. When A375P cells were then incubated with cytokines associated with keratinocytes (IL-1 and interferon β) or hepatocytes (transforming growth factor α or β), IL-1 enhanced the production of IL-8 protein, whereas TGF-β decreased its production. These data show that IL-8 expression in melanoma cells is modulated by local host factors.

Original languageEnglish (US)
Pages (from-to)2470-2475
Number of pages6
JournalCancer Research
Volume55
Issue number11
StatePublished - Jun 1 1995

Fingerprint

Interleukin-8
Melanoma
Liver
Neoplasms
Interleukin-1
Keratinocytes
Nude Mice
Messenger RNA
Neoplasm Metastasis
Cellular Microenvironment
Lung
Proteins
Hepatocyte Growth Factor
Transforming Growth Factors
Northern Blotting
Interferons
Tail
Hepatocellular Carcinoma
Veins
Spleen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gutman, M., Singh, R. K., Xie, K., Bucana, C. D., & Fidler, I. J. (1995). Regulation of Interleukin-8 Expression in Human Melanoma Cells by the Organ Environment. Cancer Research, 55(11), 2470-2475.

Regulation of Interleukin-8 Expression in Human Melanoma Cells by the Organ Environment. / Gutman, Mordechai; Singh, Rakesh K.; Xie, Keping; Bucana, Corazon D.; Fidler, Isaiah J.

In: Cancer Research, Vol. 55, No. 11, 01.06.1995, p. 2470-2475.

Research output: Contribution to journalArticle

Gutman, M, Singh, RK, Xie, K, Bucana, CD & Fidler, IJ 1995, 'Regulation of Interleukin-8 Expression in Human Melanoma Cells by the Organ Environment', Cancer Research, vol. 55, no. 11, pp. 2470-2475.
Gutman, Mordechai ; Singh, Rakesh K. ; Xie, Keping ; Bucana, Corazon D. ; Fidler, Isaiah J. / Regulation of Interleukin-8 Expression in Human Melanoma Cells by the Organ Environment. In: Cancer Research. 1995 ; Vol. 55, No. 11. pp. 2470-2475.
@article{e94a00c5af1b468296d4a0ed6f1cf6cc,
title = "Regulation of Interleukin-8 Expression in Human Melanoma Cells by the Organ Environment",
abstract = "The in vitro expression level of interleukin-8 (IL-8) correlates with the metastatic potential of human melanoma cells. The purpose of this study was to determine whether the expression level of IL-8 in human melanoma cells is influenced by the organ microenvironment A375P cells, a low metastatic human melanoma, and A375SM cells, a highly metastatic variant, were injected into the subcutis (s.c), spleen (to produce liver metastases), and lateral tail vein (to produce lung metastases) of athymic nude mice. Northern blot and immunohistochemical analyses determined that s.c. tumors, lung lesions, and liver lesions expressed high, intermediate, and low IL-8, mRNA, and protein, respectively. This differential regulation of IL-8 was not due to the size or density of the lesions or to selection of subpopulations of cells. We based this conclusion on the results of three experiments: (a) melanoma cell lines established in culture from in vivo-growing tumors exhibited similar levels of IL-8 mRNA transcripts; (b) in a crossover experiment, the level of IL-8 mRNA was always high in A375 tumors reestablished in the skin and low in the tumors reestablished in the liver, regardless of whether the melanoma cells had been first harvested from s.c. or liver tumors; and (c) A375 melanoma cells cocul-tured with human keratinocytes produced high levels of IL-8 protein, whereas A375 cells cocultured with highly differentiated human hepatoma cells produced decreased levels. When A375P cells were then incubated with cytokines associated with keratinocytes (IL-1 and interferon β) or hepatocytes (transforming growth factor α or β), IL-1 enhanced the production of IL-8 protein, whereas TGF-β decreased its production. These data show that IL-8 expression in melanoma cells is modulated by local host factors.",
author = "Mordechai Gutman and Singh, {Rakesh K.} and Keping Xie and Bucana, {Corazon D.} and Fidler, {Isaiah J.}",
year = "1995",
month = "6",
day = "1",
language = "English (US)",
volume = "55",
pages = "2470--2475",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Regulation of Interleukin-8 Expression in Human Melanoma Cells by the Organ Environment

AU - Gutman, Mordechai

AU - Singh, Rakesh K.

AU - Xie, Keping

AU - Bucana, Corazon D.

AU - Fidler, Isaiah J.

PY - 1995/6/1

Y1 - 1995/6/1

N2 - The in vitro expression level of interleukin-8 (IL-8) correlates with the metastatic potential of human melanoma cells. The purpose of this study was to determine whether the expression level of IL-8 in human melanoma cells is influenced by the organ microenvironment A375P cells, a low metastatic human melanoma, and A375SM cells, a highly metastatic variant, were injected into the subcutis (s.c), spleen (to produce liver metastases), and lateral tail vein (to produce lung metastases) of athymic nude mice. Northern blot and immunohistochemical analyses determined that s.c. tumors, lung lesions, and liver lesions expressed high, intermediate, and low IL-8, mRNA, and protein, respectively. This differential regulation of IL-8 was not due to the size or density of the lesions or to selection of subpopulations of cells. We based this conclusion on the results of three experiments: (a) melanoma cell lines established in culture from in vivo-growing tumors exhibited similar levels of IL-8 mRNA transcripts; (b) in a crossover experiment, the level of IL-8 mRNA was always high in A375 tumors reestablished in the skin and low in the tumors reestablished in the liver, regardless of whether the melanoma cells had been first harvested from s.c. or liver tumors; and (c) A375 melanoma cells cocul-tured with human keratinocytes produced high levels of IL-8 protein, whereas A375 cells cocultured with highly differentiated human hepatoma cells produced decreased levels. When A375P cells were then incubated with cytokines associated with keratinocytes (IL-1 and interferon β) or hepatocytes (transforming growth factor α or β), IL-1 enhanced the production of IL-8 protein, whereas TGF-β decreased its production. These data show that IL-8 expression in melanoma cells is modulated by local host factors.

AB - The in vitro expression level of interleukin-8 (IL-8) correlates with the metastatic potential of human melanoma cells. The purpose of this study was to determine whether the expression level of IL-8 in human melanoma cells is influenced by the organ microenvironment A375P cells, a low metastatic human melanoma, and A375SM cells, a highly metastatic variant, were injected into the subcutis (s.c), spleen (to produce liver metastases), and lateral tail vein (to produce lung metastases) of athymic nude mice. Northern blot and immunohistochemical analyses determined that s.c. tumors, lung lesions, and liver lesions expressed high, intermediate, and low IL-8, mRNA, and protein, respectively. This differential regulation of IL-8 was not due to the size or density of the lesions or to selection of subpopulations of cells. We based this conclusion on the results of three experiments: (a) melanoma cell lines established in culture from in vivo-growing tumors exhibited similar levels of IL-8 mRNA transcripts; (b) in a crossover experiment, the level of IL-8 mRNA was always high in A375 tumors reestablished in the skin and low in the tumors reestablished in the liver, regardless of whether the melanoma cells had been first harvested from s.c. or liver tumors; and (c) A375 melanoma cells cocul-tured with human keratinocytes produced high levels of IL-8 protein, whereas A375 cells cocultured with highly differentiated human hepatoma cells produced decreased levels. When A375P cells were then incubated with cytokines associated with keratinocytes (IL-1 and interferon β) or hepatocytes (transforming growth factor α or β), IL-1 enhanced the production of IL-8 protein, whereas TGF-β decreased its production. These data show that IL-8 expression in melanoma cells is modulated by local host factors.

UR - http://www.scopus.com/inward/record.url?scp=0029003286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029003286&partnerID=8YFLogxK

M3 - Article

C2 - 7758001

AN - SCOPUS:0029003286

VL - 55

SP - 2470

EP - 2475

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 11

ER -