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.
Highlights
Cancer metastases contribute to over 90% of cancer deaths
Tumor-secreted factors regulate the expression of molecules such as S100A8, S100A9, LOX, fibronectin, matrix metalloproteinases (MMPs)-9, MMP-217 that promote the recruitment of specific bone marrow-derived cells (VEGFR1+, CD11b+, CD34+), myeloid cells (CD11b+) as well as differentiated innate and adaptive immune cells[17,18]
The B16-hCXCR4-GFP cells were stained with Cell Tracker Green and allowed to migrate toward medium containing CXCL12 (300 ng/ml) or CXCL12 (5 μg/ml)-loaded gels (CLGs) loaded with 300 ng/ml CXCL12
Summary
Cancer metastases contribute to over 90% of cancer deaths. The metastatic process is a complex process that involves primary tumors, tumor microenvironment and distant organs[1,2]. CXCL12, known as (ECM) at the pre-metastatic niche, a tumor growthfavoring microenvironment developed in the absence of neoplastic cells[13,14,15], secreting inflammatory cytokines and growth factors such as CXCL12, TGF-β, S100A4, and Official journal of the Cell Death Differentiation Association. A commercially available dermal filler, HA-based gel, loaded with CXCL12 reproduced a “fake” pre-metastatic niche. The efficacy of this tool was evaluated in (i) recruiting circulating cells to be biologically characterized; (ii) trapping tumor cells and reducing metastases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
