A novel role of the CX3 CR1/CX3 CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment

E. Ferretti; M. Bertolotto; S. Deaglio; C. Tripodo; D. Ribatti; V. Audrito; F. Blengio; S. Matis; S. Zupo; D. Rossi; L. Ottonello; G. Gaidano; F. Malavasi; V. Pistoia; A. Corcione

doi:10.1038/leu.2011.88

A novel role of the CX₃ CR1/CX₃ CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment

E. Ferretti, M. Bertolotto, S. Deaglio, C. Tripodo, D. Ribatti, V. Audrito, F. Blengio, S. Matis, S. Zupo, D. Rossi, L. Ottonello, G. Gaidano, F. Malavasi, V. Pistoia, A. Corcione

Dipartimento di Medicina Traslazionale

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Several chemokines/chemokine receptors such as CCR7, CXCR4 and CXCR5 attract chronic lymphocytic leukemia (CLL) cells to specific microenvironments. Here we have investigated whether the CX₃ CR1/CX₃ CL1 axis is involved in the interaction of CLL with their microenvironment. CLL cells from 52 patients expressed surface CX₃ CR1 and CX₃ CL1 and released constitutively soluble CX₃ CL1. One third of these were attracted in vitro by soluble CX₃ CL1. CX₃ CL1-induced phosphorylation of PI3K, Erk1/2, p38, Akt and Src was involved in induction of CLL chemotaxis. Leukemic B cells upregulated CXCR4 upon incubation with CX ₃ CL1 and this was paralleled by increased chemotaxis to CXCL12. Akt phosphorylation was involved in CX₃ CL1-induced upregulation of CXCR4 on CLL. In proliferation centers from CLL lymph node and bone marrow, CX ₃ CL1 was expressed by CLL cells whereas CX₃ CR1 was detected in CLL and stromal cells. Nurselike cells (NLCs) generated from CLL patient blood co-expressed surface CX₃ CR1 and CX₃ CL1, but did not secrete soluble CX₃ CL1. Only half of NLC cell fractions were attracted in vitro by CX₃ CL1. In conclusion, the CX₃ CR1/CX₃ CL1 system may contribute to interactions between CLL cells and tumor microenvironment by increasing CXCL12-mediated attraction of leukemic cells to NLC and promoting directly adhesion of CLL cells to NLC.

Lingua originale	Inglese
pagine (da-a)	1268-1277
Numero di pagine	10
Rivista	Leukemia
Volume	25
Numero di pubblicazione	8
DOI	https://doi.org/10.1038/leu.2011.88
Stato di pubblicazione	Pubblicato - ago 2011

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10.1038/leu.2011.88

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Ferretti, E., Bertolotto, M., Deaglio, S., Tripodo, C., Ribatti, D., Audrito, V., Blengio, F., Matis, S., Zupo, S., Rossi, D., Ottonello, L., Gaidano, G., Malavasi, F., Pistoia, V., & Corcione, A. (2011). A novel role of the CX₃ CR1/CX₃ CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment. Leukemia, 25(8), 1268-1277. https://doi.org/10.1038/leu.2011.88

@article{19e3aec585944d198ca5cdce63cbdcb8,

title = "A novel role of the CX3 CR1/CX3 CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment",

abstract = "Several chemokines/chemokine receptors such as CCR7, CXCR4 and CXCR5 attract chronic lymphocytic leukemia (CLL) cells to specific microenvironments. Here we have investigated whether the CX3 CR1/CX3 CL1 axis is involved in the interaction of CLL with their microenvironment. CLL cells from 52 patients expressed surface CX3 CR1 and CX3 CL1 and released constitutively soluble CX3 CL1. One third of these were attracted in vitro by soluble CX3 CL1. CX3 CL1-induced phosphorylation of PI3K, Erk1/2, p38, Akt and Src was involved in induction of CLL chemotaxis. Leukemic B cells upregulated CXCR4 upon incubation with CX 3 CL1 and this was paralleled by increased chemotaxis to CXCL12. Akt phosphorylation was involved in CX3 CL1-induced upregulation of CXCR4 on CLL. In proliferation centers from CLL lymph node and bone marrow, CX 3 CL1 was expressed by CLL cells whereas CX3 CR1 was detected in CLL and stromal cells. Nurselike cells (NLCs) generated from CLL patient blood co-expressed surface CX3 CR1 and CX3 CL1, but did not secrete soluble CX3 CL1. Only half of NLC cell fractions were attracted in vitro by CX3 CL1. In conclusion, the CX3 CR1/CX3 CL1 system may contribute to interactions between CLL cells and tumor microenvironment by increasing CXCL12-mediated attraction of leukemic cells to NLC and promoting directly adhesion of CLL cells to NLC.",

keywords = "chemokines, chronic lymphocytic leukemia (CLL), nurselike cells (NLCs), tumor microenvironment",

author = "E. Ferretti and M. Bertolotto and S. Deaglio and C. Tripodo and D. Ribatti and V. Audrito and F. Blengio and S. Matis and S. Zupo and D. Rossi and L. Ottonello and G. Gaidano and F. Malavasi and V. Pistoia and A. Corcione",

note = "Funding Information: We thank Dr Salvatore Casciaro, from the Department of Internal Medicine, University of Genova, Italy, for providing a few CLL samples, Dr A Pistorio from the Epidemiology and Biostatistics Unit, IRCSS G. Gaslini of Genoa, Italy, for the help in statistical analysis, Dr Carla Guarnotta for the help in immunohistochemical analysis and Dr Paolo Fardin for supervising PCR experiments. The work has been supported by grants from Progetti Strategici Oncologici, Ministero della Salute 2006 to AC and VP, from AIRC to VP, and from Bando Giovani Ricercatori 2008, Ministero della Salute and AIRC to SD.",

year = "2011",

month = aug,

doi = "10.1038/leu.2011.88",

language = "English",

volume = "25",

pages = "1268--1277",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

number = "8",

}

Ferretti, E, Bertolotto, M, Deaglio, S, Tripodo, C, Ribatti, D, Audrito, V, Blengio, F, Matis, S, Zupo, S, Rossi, D, Ottonello, L, Gaidano, G, Malavasi, F, Pistoia, V & Corcione, A 2011, 'A novel role of the CX₃ CR1/CX₃ CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment', Leukemia, vol. 25, n. 8, pagg. 1268-1277. https://doi.org/10.1038/leu.2011.88

TY - JOUR

T1 - A novel role of the CX3 CR1/CX3 CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment

AU - Ferretti, E.

AU - Bertolotto, M.

AU - Deaglio, S.

AU - Tripodo, C.

AU - Ribatti, D.

AU - Audrito, V.

AU - Blengio, F.

AU - Matis, S.

AU - Zupo, S.

AU - Rossi, D.

AU - Ottonello, L.

AU - Gaidano, G.

AU - Malavasi, F.

AU - Pistoia, V.

AU - Corcione, A.

N1 - Funding Information: We thank Dr Salvatore Casciaro, from the Department of Internal Medicine, University of Genova, Italy, for providing a few CLL samples, Dr A Pistorio from the Epidemiology and Biostatistics Unit, IRCSS G. Gaslini of Genoa, Italy, for the help in statistical analysis, Dr Carla Guarnotta for the help in immunohistochemical analysis and Dr Paolo Fardin for supervising PCR experiments. The work has been supported by grants from Progetti Strategici Oncologici, Ministero della Salute 2006 to AC and VP, from AIRC to VP, and from Bando Giovani Ricercatori 2008, Ministero della Salute and AIRC to SD.

PY - 2011/8

Y1 - 2011/8

N2 - Several chemokines/chemokine receptors such as CCR7, CXCR4 and CXCR5 attract chronic lymphocytic leukemia (CLL) cells to specific microenvironments. Here we have investigated whether the CX3 CR1/CX3 CL1 axis is involved in the interaction of CLL with their microenvironment. CLL cells from 52 patients expressed surface CX3 CR1 and CX3 CL1 and released constitutively soluble CX3 CL1. One third of these were attracted in vitro by soluble CX3 CL1. CX3 CL1-induced phosphorylation of PI3K, Erk1/2, p38, Akt and Src was involved in induction of CLL chemotaxis. Leukemic B cells upregulated CXCR4 upon incubation with CX 3 CL1 and this was paralleled by increased chemotaxis to CXCL12. Akt phosphorylation was involved in CX3 CL1-induced upregulation of CXCR4 on CLL. In proliferation centers from CLL lymph node and bone marrow, CX 3 CL1 was expressed by CLL cells whereas CX3 CR1 was detected in CLL and stromal cells. Nurselike cells (NLCs) generated from CLL patient blood co-expressed surface CX3 CR1 and CX3 CL1, but did not secrete soluble CX3 CL1. Only half of NLC cell fractions were attracted in vitro by CX3 CL1. In conclusion, the CX3 CR1/CX3 CL1 system may contribute to interactions between CLL cells and tumor microenvironment by increasing CXCL12-mediated attraction of leukemic cells to NLC and promoting directly adhesion of CLL cells to NLC.

AB - Several chemokines/chemokine receptors such as CCR7, CXCR4 and CXCR5 attract chronic lymphocytic leukemia (CLL) cells to specific microenvironments. Here we have investigated whether the CX3 CR1/CX3 CL1 axis is involved in the interaction of CLL with their microenvironment. CLL cells from 52 patients expressed surface CX3 CR1 and CX3 CL1 and released constitutively soluble CX3 CL1. One third of these were attracted in vitro by soluble CX3 CL1. CX3 CL1-induced phosphorylation of PI3K, Erk1/2, p38, Akt and Src was involved in induction of CLL chemotaxis. Leukemic B cells upregulated CXCR4 upon incubation with CX 3 CL1 and this was paralleled by increased chemotaxis to CXCL12. Akt phosphorylation was involved in CX3 CL1-induced upregulation of CXCR4 on CLL. In proliferation centers from CLL lymph node and bone marrow, CX 3 CL1 was expressed by CLL cells whereas CX3 CR1 was detected in CLL and stromal cells. Nurselike cells (NLCs) generated from CLL patient blood co-expressed surface CX3 CR1 and CX3 CL1, but did not secrete soluble CX3 CL1. Only half of NLC cell fractions were attracted in vitro by CX3 CL1. In conclusion, the CX3 CR1/CX3 CL1 system may contribute to interactions between CLL cells and tumor microenvironment by increasing CXCL12-mediated attraction of leukemic cells to NLC and promoting directly adhesion of CLL cells to NLC.

KW - chemokines

KW - chronic lymphocytic leukemia (CLL)

KW - nurselike cells (NLCs)

KW - tumor microenvironment

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U2 - 10.1038/leu.2011.88

DO - 10.1038/leu.2011.88

M3 - Article

SN - 0887-6924

VL - 25

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JO - Leukemia

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