Accelerated tumor progression in mice lacking the ATP receptor P2X7

Elena Adinolfi; Marina Capece; Alessia Franceschini; Simonetta Falzoni; Anna L Giuliani; Alessandra Rotondo; Alba C Sarti; Massimo Bonora; Susanne Syberg; Domenica Corigliano; Paolo Pinton; Niklas R Jorgensen; Luigi Abelli; Laura Emionite; Lizzia Raffaghello; Vito Pistoia; Francesco Di Virgilio

doi:10.1158/0008-5472.can-14-1259

Accelerated tumor progression in mice lacking the ATP receptor P2X7

Elena Adinolfi, Marina Capece, Alessia Franceschini, Simonetta Falzoni, Anna L Giuliani, Alessandra Rotondo, Alba C Sarti, Massimo Bonora, Susanne Syberg, Domenica Corigliano, Paolo Pinton, Niklas R Jorgensen, Luigi Abelli, Laura Emionite, Lizzia Raffaghello, Vito Pistoia, Francesco Di Virgilio

Department of Clinical Medicine

78 Citations (Scopus)

Abstract

The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammationand immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, comparedwith wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion.

Original language	English
Journal	Cancer Research
Volume	75
Issue number	4
Pages (from-to)	635-44
Number of pages	10
ISSN	0008-5472
DOIs	https://doi.org/10.1158/0008-5472.can-14-1259
Publication status	Published - 15 Feb 2015

Keywords

Adenosine Triphosphate
Animals
Colonic Neoplasms
Gene Expression Regulation, Neoplastic
Humans
Immunity, Innate
Interleukin-1beta
Macrophages
Melanoma, Experimental
Mice
Receptors, Purinergic P2X7
Vascular Endothelial Growth Factor A

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Adinolfi, E., Capece, M., Franceschini, A., Falzoni, S., Giuliani, A. L., Rotondo, A., Sarti, A. C., Bonora, M., Syberg, S., Corigliano, D., Pinton, P., Jorgensen, N. R., Abelli, L., Emionite, L., Raffaghello, L., Pistoia, V., & Di Virgilio, F. (2015). Accelerated tumor progression in mice lacking the ATP receptor P2X7. Cancer Research, 75(4), 635-44. https://doi.org/10.1158/0008-5472.can-14-1259

Adinolfi, E, Capece, M, Franceschini, A, Falzoni, S, Giuliani, AL, Rotondo, A, Sarti, AC, Bonora, M, Syberg, S, Corigliano, D, Pinton, P, Jorgensen, NR, Abelli, L, Emionite, L, Raffaghello, L, Pistoia, V & Di Virgilio, F 2015, 'Accelerated tumor progression in mice lacking the ATP receptor P2X7', Cancer Research, vol. 75, no. 4, pp. 635-44. https://doi.org/10.1158/0008-5472.can-14-1259

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title = "Accelerated tumor progression in mice lacking the ATP receptor P2X7",

abstract = "The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammationand immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, comparedwith wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion.",

keywords = "Adenosine Triphosphate, Animals, Colonic Neoplasms, Gene Expression Regulation, Neoplastic, Humans, Immunity, Innate, Interleukin-1beta, Macrophages, Melanoma, Experimental, Mice, Receptors, Purinergic P2X7, Vascular Endothelial Growth Factor A",

author = "Elena Adinolfi and Marina Capece and Alessia Franceschini and Simonetta Falzoni and Giuliani, {Anna L} and Alessandra Rotondo and Sarti, {Alba C} and Massimo Bonora and Susanne Syberg and Domenica Corigliano and Paolo Pinton and Jorgensen, {Niklas R} and Luigi Abelli and Laura Emionite and Lizzia Raffaghello and Vito Pistoia and {Di Virgilio}, Francesco",

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T1 - Accelerated tumor progression in mice lacking the ATP receptor P2X7

AU - Adinolfi, Elena

AU - Capece, Marina

AU - Franceschini, Alessia

AU - Falzoni, Simonetta

AU - Giuliani, Anna L

AU - Rotondo, Alessandra

AU - Sarti, Alba C

AU - Bonora, Massimo

AU - Syberg, Susanne

AU - Corigliano, Domenica

AU - Pinton, Paolo

AU - Jorgensen, Niklas R

AU - Abelli, Luigi

AU - Emionite, Laura

AU - Raffaghello, Lizzia

AU - Pistoia, Vito

AU - Di Virgilio, Francesco

PY - 2015/2/15

Y1 - 2015/2/15

N2 - The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammationand immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, comparedwith wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion.

AB - The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammationand immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, comparedwith wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion.

KW - Adenosine Triphosphate

KW - Animals

KW - Colonic Neoplasms

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunity, Innate

KW - Interleukin-1beta

KW - Macrophages

KW - Melanoma, Experimental

KW - Mice

KW - Receptors, Purinergic P2X7

KW - Vascular Endothelial Growth Factor A

U2 - 10.1158/0008-5472.can-14-1259

DO - 10.1158/0008-5472.can-14-1259

M3 - Journal article

C2 - 25542861

SN - 0008-5472

VL - 75

SP - 635

EP - 644

JO - Cancer Research

JF - Cancer Research

IS - 4

ER -

Accelerated tumor progression in mice lacking the ATP receptor P2X7

Abstract

Keywords

UN SDGs

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