CXCR4+ circulating tumor cells (CTCs) accumulate in subcutaneous, immune suppressive, CXCL12-loaded-hydrogel
Circulating tumor cells (CTCs) sensing the chemokine CXCL12 and invading hyaluronic acid hydrogel (CXCL12 loaded hydrogel, CLG) might display metastatic attitude. CLG recovered-human lung (H460, A549), and ovarian cancer cells (IGROV-1) overexpressed the CXCL12 receptor, CXCR4, developed larger spheres and activate transcriptional programs of invasion and stemness. Interestingly, CLG-U87 glioblastoma cells highly expressed EpCAM and significantly upregulated the very specific NGFR, NTS, AQP1 and CMKLR1 genes, associated with cell proliferation, migration/invasion and metastasis. In a syngeneic model, subcutaneous CLG significantly attracted GFP-Lewis lung carcinoma (LLC) cells impairing lung colonization within four hours from cell injection and up to twenty-one days. In lung, M1 macrophages rapidly increased post cancer cells injection while M2 prevailed after 10 days (T10). Neutrophils (Ly6G high and Ly6G low ) infiltrated the lungs after ten days from cells injection with late expansion of immature Ly6G low . According to lung niche, Empty gel (EG) and CLG were early infiltrated by macrophages and later by neutrophils. CLG generated an immunosuppressive environment defined by M1/M2/Ly6G low able to capture and divert metastatic CTCs from the lung colonization.
Authors
- Crescenzo D’Alterio (ORCID: https://orcid.org/0000-0003-0275-3367)
- Caterina Ieranò (ORCID: https://orcid.org/0000-0003-3138-1873)
- Giulia Bertolini (ORCID: https://orcid.org/0000-0002-8495-4594)
- Stefania Scala (ORCID: https://orcid.org/0000-0001-9524-2616)
- Marco Gentili (ORCID: https://orcid.org/0000-0002-2305-4488)
- Luigi Portella (ORCID: https://orcid.org/0000-0002-8679-3309)
- Anna Maria Trotta (ORCID: https://orcid.org/0000-0003-4110-2057)
- Luca Roz (ORCID: https://orcid.org/0000-0001-5817-7149)
- Roberto Pacelli (ORCID: https://orcid.org/0000-0002-2048-7675)
- Roberta Sulsenti (ORCID: https://orcid.org/0000-0002-2247-056X)
- Sara Santagata (ORCID: https://orcid.org/0000-0001-8680-084X)
- Dario Righelli (ORCID: https://orcid.org/0000-0003-1504-3583)
- Giuseppe Guardascione (ORCID: https://orcid.org/0000-0003-4272-7948)
- Francesca Bruzzese (ORCID: https://orcid.org/0000-0001-7741-9086)
- Dario Guido Di Febbraro
- Ilaria Assunta Parisi (ORCID: https://orcid.org/0009-0008-5854-9924)
- Antonio Luciano
- Giuseppina Rea
- Giuseppe Palma
- Antonella De Luca
Institutions
- Central Institute for Experimental Animals (JP)
- Microelectronica (Romania) (RO)
- Federico II University Hospital (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- University of Naples Federico II (IT)
- Epigenomics (Germany) (DE)
Publication Details
- Journal
- Materials Today Bio
- Published
- 2026-09-04
- DOI
- https://doi.org/10.1016/j.mtbio.2026.103648
- Primary Topic
- Chemokine receptors and signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00