Development of distant metastasis relies on interactions between cancer and stromal cells. CXCL12, also known as stromal-derived factor 1α (SDF-1α), is a major chemokine constitutively secreted in bone marrow, lymph nodes, liver and lung, playing a critical role in the migration and seeding of neoplastic cells. CXCL12 activates the CXCR4 receptor that is overexpressed in several human cancer cells. Recent evidence reveals that tumors induce pre-metastatic niches in target organ producing tumor-derived factors. Pre-metastatic niches represent a tumor growth-favoring microenvironment in absence of cancer cells. A commercially available dermal filler, hyaluronic acid (HA) -based gel, loaded with CXCL12 (CLG) reproduced a "fake" pre-metastatic niche. In vitro, B16-hCXCR4-GFP, human cxcr4 expressing murine melanoma cells efficiently migrated toward CLG. In vivo, CLGs and empty gels (EGs) were subcutaneously injected into C57BL/6 mice and 5 days later B16-hCXCR4-GFP cells were intravenously inoculated. CLGs were able to recruit a significantly higher number of B16-hCXCR4-GFP cells as compared to EGs, with reduced lung metastasis in mice carrying CLG. CLG were infiltrated by higher number of CD45-positive leukocytes, mainly neutrophils CD11b+Ly6G+ cells, myeloid CD11b+Ly6G- and macrophages F4/80. CLG recovered cells recapitulated the features of B16-hCXCR4-GFP (epithelial, melanin rich, MELAN A/ S100/ c-Kit/CXCR4 pos; α-SMA neg). Thus a HA-based dermal filler loaded with CXCL12 can attract and trap CXCR4+tumor cells. The CLG trapped cells can be recovered and biologically characterized. As a corollary, a reduction in CXCR4 dependent lung metastasis was detected.

CXCL12 loaded-dermal filler captures CXCR4 expressing melanoma circulating tumor cells / Ieranò, Caterina; D'Alterio, Crescenzo; Giarra, Simona; Napolitano, Maria; Rea, Giuseppina; Portella, Luigi; Santagata, Assunta; Trotta, Anna Maria; Barbieri, Antonio; Campani, Virginia; Luciano, Antonio; Arra, Claudio; Anniciello, Anna Maria; Botti, Gerardo; Mayol, Laura; De Rosa, Giuseppe; Pacelli, Roberto; Scala, Stefania. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 10:8(2019), p. 562. [10.1038/s41419-019-1796-6]

CXCL12 loaded-dermal filler captures CXCR4 expressing melanoma circulating tumor cells

Giarra, Simona;Napolitano, Maria;Rea, Giuseppina;Barbieri, Antonio;Campani, Virginia;Anniciello, Anna Maria;Mayol, Laura;De Rosa, Giuseppe;Pacelli, Roberto;
2019

Abstract

Development of distant metastasis relies on interactions between cancer and stromal cells. CXCL12, also known as stromal-derived factor 1α (SDF-1α), is a major chemokine constitutively secreted in bone marrow, lymph nodes, liver and lung, playing a critical role in the migration and seeding of neoplastic cells. CXCL12 activates the CXCR4 receptor that is overexpressed in several human cancer cells. Recent evidence reveals that tumors induce pre-metastatic niches in target organ producing tumor-derived factors. Pre-metastatic niches represent a tumor growth-favoring microenvironment in absence of cancer cells. A commercially available dermal filler, hyaluronic acid (HA) -based gel, loaded with CXCL12 (CLG) reproduced a "fake" pre-metastatic niche. In vitro, B16-hCXCR4-GFP, human cxcr4 expressing murine melanoma cells efficiently migrated toward CLG. In vivo, CLGs and empty gels (EGs) were subcutaneously injected into C57BL/6 mice and 5 days later B16-hCXCR4-GFP cells were intravenously inoculated. CLGs were able to recruit a significantly higher number of B16-hCXCR4-GFP cells as compared to EGs, with reduced lung metastasis in mice carrying CLG. CLG were infiltrated by higher number of CD45-positive leukocytes, mainly neutrophils CD11b+Ly6G+ cells, myeloid CD11b+Ly6G- and macrophages F4/80. CLG recovered cells recapitulated the features of B16-hCXCR4-GFP (epithelial, melanin rich, MELAN A/ S100/ c-Kit/CXCR4 pos; α-SMA neg). Thus a HA-based dermal filler loaded with CXCL12 can attract and trap CXCR4+tumor cells. The CLG trapped cells can be recovered and biologically characterized. As a corollary, a reduction in CXCR4 dependent lung metastasis was detected.
2019
CXCL12 loaded-dermal filler captures CXCR4 expressing melanoma circulating tumor cells / Ieranò, Caterina; D'Alterio, Crescenzo; Giarra, Simona; Napolitano, Maria; Rea, Giuseppina; Portella, Luigi; Santagata, Assunta; Trotta, Anna Maria; Barbieri, Antonio; Campani, Virginia; Luciano, Antonio; Arra, Claudio; Anniciello, Anna Maria; Botti, Gerardo; Mayol, Laura; De Rosa, Giuseppe; Pacelli, Roberto; Scala, Stefania. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 10:8(2019), p. 562. [10.1038/s41419-019-1796-6]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/788511
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