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 language | English |
|---|---|
| Pages (from-to) | 2427-2433 |
| Number of pages | 7 |
| Journal | Clinical Cancer Research |
| Volume | 12 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Apr 15 2006 |
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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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=33646426383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646426383&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-1940
DO - 10.1158/1078-0432.CCR-05-1940
M3 - Article
C2 - 16638848
AN - SCOPUS:33646426383
VL - 12
SP - 2427
EP - 2433
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 8
ER -