Human melanoma metastases express functional CXCR4

Stefania Scala, Paola Giuliano, Paolo A. Ascierto, Caterina Ieranò, Renato Franco, Maria Napolitano, Alessandro Ottaiano, Maria L. Lombardi, Monica Luongo, Ester Simeone, Daniele Castiglia, Francesca Mauro, Ileana De Michele, Rosa Calemma, Gerardo Botti, Corrado Caracò, Gianfranco Nicoletti, Rocco A. Satriano, Giuseppe Castello

Research output: Contribution to journalArticle

Abstract

Purpose: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. Experimental Design: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. Results: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 μmol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. Conclusions: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.

Original languageEnglish
Pages (from-to)2427-2433
Number of pages7
JournalClinical Cancer Research
Volume12
Issue number8
DOIs
Publication statusPublished - Apr 15 2006

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Melanoma
Neoplasm Metastasis
Cell Line
Chemokine Receptors
Apoptosis
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Serum
Immunoblotting
Reverse Transcription
Fluorescent Antibody Technique
Research Design
Immunohistochemistry
Phosphorylation
Ligands
Polymerase Chain Reaction
Skin
Growth
JM 3100

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Human melanoma metastases express functional CXCR4. / Scala, Stefania; Giuliano, Paola; Ascierto, Paolo A.; Ieranò, Caterina; Franco, Renato; Napolitano, Maria; Ottaiano, Alessandro; Lombardi, Maria L.; Luongo, Monica; Simeone, Ester; Castiglia, Daniele; Mauro, Francesca; De Michele, Ileana; Calemma, Rosa; Botti, Gerardo; Caracò, Corrado; Nicoletti, Gianfranco; Satriano, Rocco A.; Castello, Giuseppe.

In: Clinical Cancer Research, Vol. 12, No. 8, 15.04.2006, p. 2427-2433.

Research output: Contribution to journalArticle

Scala, S, Giuliano, P, Ascierto, PA, Ieranò, C, Franco, R, Napolitano, M, Ottaiano, A, Lombardi, ML, Luongo, M, Simeone, E, Castiglia, D, Mauro, F, De Michele, I, Calemma, R, Botti, G, Caracò, C, Nicoletti, G, Satriano, RA & Castello, G 2006, 'Human melanoma metastases express functional CXCR4', Clinical Cancer Research, vol. 12, no. 8, pp. 2427-2433. https://doi.org/10.1158/1078-0432.CCR-05-1940
Scala, Stefania ; Giuliano, Paola ; Ascierto, Paolo A. ; Ieranò, Caterina ; Franco, Renato ; Napolitano, Maria ; Ottaiano, Alessandro ; Lombardi, Maria L. ; Luongo, Monica ; Simeone, Ester ; Castiglia, Daniele ; Mauro, Francesca ; De Michele, Ileana ; Calemma, Rosa ; Botti, Gerardo ; Caracò, Corrado ; Nicoletti, Gianfranco ; Satriano, Rocco A. ; Castello, Giuseppe. / Human melanoma metastases express functional CXCR4. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 8. pp. 2427-2433.
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title = "Human melanoma metastases express functional CXCR4",
abstract = "Purpose: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. Experimental Design: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. Results: CXCR4 expression was detected in 33 out of 63 (52.4{\%}) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90{\%} of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65{\%} of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1{\%} serum) and serum-free culture conditions; AMD3100 (1 μmol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. Conclusions: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.",
author = "Stefania Scala and Paola Giuliano and Ascierto, {Paolo A.} and Caterina Ieran{\`o} and Renato Franco and Maria Napolitano and Alessandro Ottaiano and Lombardi, {Maria L.} and Monica Luongo and Ester Simeone and Daniele Castiglia and Francesca Mauro and {De Michele}, Ileana and Rosa Calemma and Gerardo Botti and Corrado Carac{\`o} and Gianfranco Nicoletti and Satriano, {Rocco A.} and Giuseppe Castello",
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T1 - Human melanoma metastases express functional CXCR4

AU - Scala, Stefania

AU - Giuliano, Paola

AU - Ascierto, Paolo A.

AU - Ieranò, Caterina

AU - Franco, Renato

AU - Napolitano, Maria

AU - Ottaiano, Alessandro

AU - Lombardi, Maria L.

AU - Luongo, Monica

AU - Simeone, Ester

AU - Castiglia, Daniele

AU - Mauro, Francesca

AU - De Michele, Ileana

AU - Calemma, Rosa

AU - Botti, Gerardo

AU - Caracò, Corrado

AU - Nicoletti, Gianfranco

AU - Satriano, Rocco A.

AU - Castello, Giuseppe

PY - 2006/4/15

Y1 - 2006/4/15

N2 - Purpose: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. Experimental Design: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. Results: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 μmol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. Conclusions: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.

AB - Purpose: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. Experimental Design: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. Results: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 μmol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. Conclusions: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.

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