Modulation of complement activation by pentraxin-3 in prostate cancer
Abstract Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possib...
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Nature Portfolio
2020
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oai:doaj.org-article:f215d0e804c34c8aa63a3662102796a02021-12-02T15:10:24ZModulation of complement activation by pentraxin-3 in prostate cancer10.1038/s41598-020-75376-z2045-2322https://doaj.org/article/f215d0e804c34c8aa63a3662102796a02020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-75376-zhttps://doaj.org/toc/2045-2322Abstract Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12–36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration.Giovanni StalloneGiuseppe Stefano NettiLuigi CormioGiuseppe CastellanoBarbara InfantePaola PontrelliChiara DivellaOscar SelvaggioFederica SpadaccinoElena RanieriFrancesca SanguedolceAntonio PennellaLoreto GesualdoGiuseppe CarrieriGiuseppe GrandalianoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) |
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Medicine R Science Q |
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Medicine R Science Q Giovanni Stallone Giuseppe Stefano Netti Luigi Cormio Giuseppe Castellano Barbara Infante Paola Pontrelli Chiara Divella Oscar Selvaggio Federica Spadaccino Elena Ranieri Francesca Sanguedolce Antonio Pennella Loreto Gesualdo Giuseppe Carrieri Giuseppe Grandaliano Modulation of complement activation by pentraxin-3 in prostate cancer |
| description |
Abstract Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12–36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration. |
| format |
article |
| author |
Giovanni Stallone Giuseppe Stefano Netti Luigi Cormio Giuseppe Castellano Barbara Infante Paola Pontrelli Chiara Divella Oscar Selvaggio Federica Spadaccino Elena Ranieri Francesca Sanguedolce Antonio Pennella Loreto Gesualdo Giuseppe Carrieri Giuseppe Grandaliano |
| author_facet |
Giovanni Stallone Giuseppe Stefano Netti Luigi Cormio Giuseppe Castellano Barbara Infante Paola Pontrelli Chiara Divella Oscar Selvaggio Federica Spadaccino Elena Ranieri Francesca Sanguedolce Antonio Pennella Loreto Gesualdo Giuseppe Carrieri Giuseppe Grandaliano |
| author_sort |
Giovanni Stallone |
| title |
Modulation of complement activation by pentraxin-3 in prostate cancer |
| title_short |
Modulation of complement activation by pentraxin-3 in prostate cancer |
| title_full |
Modulation of complement activation by pentraxin-3 in prostate cancer |
| title_fullStr |
Modulation of complement activation by pentraxin-3 in prostate cancer |
| title_full_unstemmed |
Modulation of complement activation by pentraxin-3 in prostate cancer |
| title_sort |
modulation of complement activation by pentraxin-3 in prostate cancer |
| publisher |
Nature Portfolio |
| publishDate |
2020 |
| url |
https://doaj.org/article/f215d0e804c34c8aa63a3662102796a0 |
| work_keys_str_mv |
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