The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination
Abstract The lymphatic vascular system represents a major route for dissemination of several solid tumors, including melanoma. Even though the members of the Vascular Endothelial Growth Factor family VEGF-C and VEGF-A have been shown to drive tumor lymphangiogenesis, experimental evidence indicates...
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Experimental Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40164-022-00330-w |
| _version_ | 1811233681306550272 |
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| author | Marta Turati Arianna Giacomini Sara Rezzola Federica Maccarinelli Giorgia Gazzaroli Sonia Valentino Barbara Bottazzi Marco Presta Roberto Ronca |
| author_facet | Marta Turati Arianna Giacomini Sara Rezzola Federica Maccarinelli Giorgia Gazzaroli Sonia Valentino Barbara Bottazzi Marco Presta Roberto Ronca |
| author_sort | Marta Turati |
| collection | DOAJ |
| description | Abstract The lymphatic vascular system represents a major route for dissemination of several solid tumors, including melanoma. Even though the members of the Vascular Endothelial Growth Factor family VEGF-C and VEGF-A have been shown to drive tumor lymphangiogenesis, experimental evidence indicates that also the pro-angiogenic factor Fibroblast Growth Factor-2 (FGF2) may play a role in the lymphangiogenic switch by triggering the activation of lymphatic endothelial cells (LECs) in cooperation with VEGFs. The soluble pattern recognition receptor Long Pentraxin 3 (PTX3) acts as a natural FGF trap, thus exerting an oncosuppressive role in FGF-dependent tumors. Here, the capacity of PTX3 to modulate lymphangiogenesis was assessed in vitro and in vivo. The results demonstrate that recombinant human PTX3 inhibits the lymphangiogenic activity exerted by the VEGF-A/FGF2/sphingosine-1-phosphate (VFS) cocktail on human and murine LECs. In keeping with in vitro data, a reduced lymphangiogenic response was observed in a lymphangiogenic Matrigel plug assay following the subcutaneous injection of the VFS cocktail in PTX3-overexpressing transgenic TgN(Tie2-hPTX3) mice when compared to wild-type or Ptx3 null animals. Accordingly, the capacity of B16F10-VEGFC-luc melanoma cells to colonize the primary tumor-draining lymph node after grafting into the foot pad was dramatically impaired in PTX3-overexpressing mice. Together with the observation that both the VFS cocktail and melanoma cell conditioned media caused a significant downregulation of PTX3 expression in LECs, these data indicate that the FGF trap activity of PTX3 may exert a key effect in the modulation of lymphangiogenesis and tumor metastatic dissemination. |
| first_indexed | 2024-04-12T11:23:47Z |
| format | Article |
| id | doaj.art-cc0101716d6b4c9a8cfab94cd16600c0 |
| institution | Directory Open Access Journal |
| issn | 2162-3619 |
| language | English |
| last_indexed | 2024-04-12T11:23:47Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj.art-cc0101716d6b4c9a8cfab94cd16600c02022-12-22T03:35:17ZengBMCExperimental Hematology & Oncology2162-36192022-11-011111610.1186/s40164-022-00330-wThe natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic disseminationMarta Turati0Arianna Giacomini1Sara Rezzola2Federica Maccarinelli3Giorgia Gazzaroli4Sonia Valentino5Barbara Bottazzi6Marco Presta7Roberto Ronca8Department of Molecular and Translational Medicine, University of BresciaDepartment of Molecular and Translational Medicine, University of BresciaDepartment of Molecular and Translational Medicine, University of BresciaDepartment of Molecular and Translational Medicine, University of BresciaDepartment of Molecular and Translational Medicine, University of BresciaIRCCS Humanitas Research HospitalIRCCS Humanitas Research HospitalDepartment of Molecular and Translational Medicine, University of BresciaDepartment of Molecular and Translational Medicine, University of BresciaAbstract The lymphatic vascular system represents a major route for dissemination of several solid tumors, including melanoma. Even though the members of the Vascular Endothelial Growth Factor family VEGF-C and VEGF-A have been shown to drive tumor lymphangiogenesis, experimental evidence indicates that also the pro-angiogenic factor Fibroblast Growth Factor-2 (FGF2) may play a role in the lymphangiogenic switch by triggering the activation of lymphatic endothelial cells (LECs) in cooperation with VEGFs. The soluble pattern recognition receptor Long Pentraxin 3 (PTX3) acts as a natural FGF trap, thus exerting an oncosuppressive role in FGF-dependent tumors. Here, the capacity of PTX3 to modulate lymphangiogenesis was assessed in vitro and in vivo. The results demonstrate that recombinant human PTX3 inhibits the lymphangiogenic activity exerted by the VEGF-A/FGF2/sphingosine-1-phosphate (VFS) cocktail on human and murine LECs. In keeping with in vitro data, a reduced lymphangiogenic response was observed in a lymphangiogenic Matrigel plug assay following the subcutaneous injection of the VFS cocktail in PTX3-overexpressing transgenic TgN(Tie2-hPTX3) mice when compared to wild-type or Ptx3 null animals. Accordingly, the capacity of B16F10-VEGFC-luc melanoma cells to colonize the primary tumor-draining lymph node after grafting into the foot pad was dramatically impaired in PTX3-overexpressing mice. Together with the observation that both the VFS cocktail and melanoma cell conditioned media caused a significant downregulation of PTX3 expression in LECs, these data indicate that the FGF trap activity of PTX3 may exert a key effect in the modulation of lymphangiogenesis and tumor metastatic dissemination.https://doi.org/10.1186/s40164-022-00330-wLong pentraxin 3LymphangiogenesisFibroblast growth factorMelanomaMetastasis |
| spellingShingle | Marta Turati Arianna Giacomini Sara Rezzola Federica Maccarinelli Giorgia Gazzaroli Sonia Valentino Barbara Bottazzi Marco Presta Roberto Ronca The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination Experimental Hematology & Oncology Long pentraxin 3 Lymphangiogenesis Fibroblast growth factor Melanoma Metastasis |
| title | The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination |
| title_full | The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination |
| title_fullStr | The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination |
| title_full_unstemmed | The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination |
| title_short | The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination |
| title_sort | natural fgf trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination |
| topic | Long pentraxin 3 Lymphangiogenesis Fibroblast growth factor Melanoma Metastasis |
| url | https://doi.org/10.1186/s40164-022-00330-w |
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