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P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis
by
Di Virgilio, Francesco
, Gallo, Graziana
, Ulivi, Paola
, Antonioli, Luca
, Adinolfi, Elena
, Pegoraro, Anna
, De Marchi, Elena
, Chioccioli, Sofia
, Alfieri, Letizia
, Ruo, Luigia
, Passardi, Alessandro
, Caderni, Giovanna
, Zanoni, Michele
, Grignolo, Marianna
in
13/21
/ 13/51
/ 14/19
/ 38/5
/ 38/77
/ 42/109
/ 5'-Nucleotidase - genetics
/ 5'-Nucleotidase - metabolism
/ 631/67/1504/1885/1393
/ 631/67/322
/ 631/67/327
/ 631/80/86/2372
/ 631/80/86/820
/ 64/60
/ 82/80
/ 96/95
/ Adenomatous polyposis coli
/ Adenosine
/ Adenosine A2A receptors
/ Animals
/ Antibodies
/ Antigens, CD - metabolism
/ Apyrase - genetics
/ Apyrase - metabolism
/ Biochemistry
/ Biomedical and Life Sciences
/ Cancer therapies
/ CD73 antigen
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Colon
/ Colon cancer
/ Colonic Neoplasms - drug therapy
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Colonic Neoplasms - pathology
/ Drug development
/ Extracellular vesicles
/ Extracellular Vesicles - drug effects
/ Extracellular Vesicles - metabolism
/ Female
/ GPI-Linked Proteins
/ Humans
/ Immunology
/ Life Sciences
/ Male
/ Medical innovations
/ Medical prognosis
/ Medical research
/ Melanoma
/ Metastases
/ Metastasis
/ Mice
/ Microscopy
/ Neoplasm Metastasis
/ Rats
/ Receptor, Adenosine A2A - genetics
/ Receptor, Adenosine A2A - metabolism
/ Receptors, Purinergic P2X7 - genetics
/ Receptors, Purinergic P2X7 - metabolism
/ Signal Transduction
/ Therapeutic targets
/ Tumors
2025
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P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis
by
Di Virgilio, Francesco
, Gallo, Graziana
, Ulivi, Paola
, Antonioli, Luca
, Adinolfi, Elena
, Pegoraro, Anna
, De Marchi, Elena
, Chioccioli, Sofia
, Alfieri, Letizia
, Ruo, Luigia
, Passardi, Alessandro
, Caderni, Giovanna
, Zanoni, Michele
, Grignolo, Marianna
in
13/21
/ 13/51
/ 14/19
/ 38/5
/ 38/77
/ 42/109
/ 5'-Nucleotidase - genetics
/ 5'-Nucleotidase - metabolism
/ 631/67/1504/1885/1393
/ 631/67/322
/ 631/67/327
/ 631/80/86/2372
/ 631/80/86/820
/ 64/60
/ 82/80
/ 96/95
/ Adenomatous polyposis coli
/ Adenosine
/ Adenosine A2A receptors
/ Animals
/ Antibodies
/ Antigens, CD - metabolism
/ Apyrase - genetics
/ Apyrase - metabolism
/ Biochemistry
/ Biomedical and Life Sciences
/ Cancer therapies
/ CD73 antigen
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Colon
/ Colon cancer
/ Colonic Neoplasms - drug therapy
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Colonic Neoplasms - pathology
/ Drug development
/ Extracellular vesicles
/ Extracellular Vesicles - drug effects
/ Extracellular Vesicles - metabolism
/ Female
/ GPI-Linked Proteins
/ Humans
/ Immunology
/ Life Sciences
/ Male
/ Medical innovations
/ Medical prognosis
/ Medical research
/ Melanoma
/ Metastases
/ Metastasis
/ Mice
/ Microscopy
/ Neoplasm Metastasis
/ Rats
/ Receptor, Adenosine A2A - genetics
/ Receptor, Adenosine A2A - metabolism
/ Receptors, Purinergic P2X7 - genetics
/ Receptors, Purinergic P2X7 - metabolism
/ Signal Transduction
/ Therapeutic targets
/ Tumors
2025
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P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis
by
Di Virgilio, Francesco
, Gallo, Graziana
, Ulivi, Paola
, Antonioli, Luca
, Adinolfi, Elena
, Pegoraro, Anna
, De Marchi, Elena
, Chioccioli, Sofia
, Alfieri, Letizia
, Ruo, Luigia
, Passardi, Alessandro
, Caderni, Giovanna
, Zanoni, Michele
, Grignolo, Marianna
in
13/21
/ 13/51
/ 14/19
/ 38/5
/ 38/77
/ 42/109
/ 5'-Nucleotidase - genetics
/ 5'-Nucleotidase - metabolism
/ 631/67/1504/1885/1393
/ 631/67/322
/ 631/67/327
/ 631/80/86/2372
/ 631/80/86/820
/ 64/60
/ 82/80
/ 96/95
/ Adenomatous polyposis coli
/ Adenosine
/ Adenosine A2A receptors
/ Animals
/ Antibodies
/ Antigens, CD - metabolism
/ Apyrase - genetics
/ Apyrase - metabolism
/ Biochemistry
/ Biomedical and Life Sciences
/ Cancer therapies
/ CD73 antigen
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Colon
/ Colon cancer
/ Colonic Neoplasms - drug therapy
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Colonic Neoplasms - pathology
/ Drug development
/ Extracellular vesicles
/ Extracellular Vesicles - drug effects
/ Extracellular Vesicles - metabolism
/ Female
/ GPI-Linked Proteins
/ Humans
/ Immunology
/ Life Sciences
/ Male
/ Medical innovations
/ Medical prognosis
/ Medical research
/ Melanoma
/ Metastases
/ Metastasis
/ Mice
/ Microscopy
/ Neoplasm Metastasis
/ Rats
/ Receptor, Adenosine A2A - genetics
/ Receptor, Adenosine A2A - metabolism
/ Receptors, Purinergic P2X7 - genetics
/ Receptors, Purinergic P2X7 - metabolism
/ Signal Transduction
/ Therapeutic targets
/ Tumors
2025
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P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis
Journal Article
P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis
2025
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Overview
Extracellular vesicle-driven cancer metastasis represents a therapeutic challenge due to the lack of effective blocking drugs. Our study shows that activation of the P2X7 receptor on colon carcinoma cells causes the release of vesicles carrying CD39 and CD73 ectonucleotidases. These vesicles increase ATP and adenosine levels and, when in vivo administered, significantly enhance colon carcinoma metastasis and circulating levels of vesicles after fourteen days from their injection. Blocking P2X7 prevents vesicular release and substantially reduces vesicle-mediated tumor spreading, positioning P2X7 as a promising therapeutic target for inhibiting extracellular vesicle-mediated dissemination in colon cancer. Additionally, these vesicles upregulate the expression of P2X7 and A2A receptors within the metastatic niche. Antagonists of P2X7 and A2A used alone or in combination effectively inhibit tumor growth in vivo, decreasing metastasis engraftment and IL-17 and IL-23 release. Interestingly, the levels of both cytokines were also reduced by combined P2X7 and A2A blockade in non-tumor-bearing mice. Moreover, P2X7 and A2A upraise in metastatic and
APC
-mutated colon carcinoma patients and in
Apc
-disrupted rats. Our findings shed light on the crosstalk of P2X7/CD73/CD39 and A2A in colon cancer metastasis. We propose a novel mechanism facilitating metastatic dissemination and an innovative therapeutic strategy to target receptor signaling and vesicular release.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/51
/ 14/19
/ 38/5
/ 38/77
/ 42/109
/ 5'-Nucleotidase - metabolism
/ 64/60
/ 82/80
/ 96/95
/ Animals
/ Biomedical and Life Sciences
/ Colon
/ Colonic Neoplasms - drug therapy
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Colonic Neoplasms - pathology
/ Extracellular Vesicles - drug effects
/ Extracellular Vesicles - metabolism
/ Female
/ Humans
/ Male
/ Melanoma
/ Mice
/ Rats
/ Receptor, Adenosine A2A - genetics
/ Receptor, Adenosine A2A - metabolism
/ Receptors, Purinergic P2X7 - genetics
/ Receptors, Purinergic P2X7 - metabolism
/ Tumors
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