Abstract 5194: In vivo capture of early metastatic cells through a CXCL12 loaded-dermal filler

Abstract

Abstract The chemokine CXCL12 and its receptor CXCR4 are critical for orienting and seeding cells in metastatic sites. To distract CXCR4 expressing circulating tumor cells (CTCs) a “fake” pre-metastatic niche was built with a hyaluronic acid based dermal filler hydrogel-CXCL12-loaded (CLG). CXCR4 expressing human T leukemia cells, CCRF-CEM, and murine melanoma cells human CXCR4 transduced, B16-hCXCR4-GFP, were evaluated for migration in vitro toward CLG. CLGs and EGs (empty gels) were subcutaneously injected in C57BL/6 mice and five days later B16-hCXCR4-GFP (5x105 cells) were intravenously injected. Twenty two days later mice were euthanized and hydrogels recovered. Gel trapped cells were recovered through ialuronidase digestion of the gels and lungs were analyzed to detect metastases. Circulating tumor cells (CD45neg/hCXCR4 plus/GFP plus) were assessed in the blood at day 10 and 22 from cells injection. In vitro, CEM and B16-hCXCR4-GFP cells more efficiently migrated toward CLG compared with EG. In vivo, a significantly higher number of B16-hCXCR4-GFP tumor cells was detected within the CLGs compared with EGs, indicating that the CXCL12 in hydrogel enabled recruitment of tumor cells. Concomitantly, lung metastases were significantly reduced in mice carrying CLG, but not EG, as assessed by reduced B16-hCXCR4-GFP positive tumor cells in the lung (75% reduction in lung metastases in mice carrying CLG; p<0.05). CLG recovered cells by hydrogel enzymatic digestion recapitulated the features of melanoma cell line B16-hCXCR4-GFP (epithelial, melanin rich, MELAN A/ S100/ c-kit/CXCR4 +; α-SMA -). CTCs, evaluated at 10 and at 22 days post cells injection, significantly increased in CLG carrying mice compared to EG carrying mice. Our study suggests that a hyaluronic acid (HA) hydrogel, commercially used as dermal filler, loaded with CXCL12 can divert CXCR4 positive circulating tumor cells B16-hCXCR4-GFP. The cells trapped in the CLG can be recovered and characterized. As a corollary, a reduction of CXCR4 dependent lung metastasis was detected. It suggests that hydrogel-CXCL12 trap may be a therapeutic and diagnostic tool to recover and analyze the biology of circulating tumor cells. Citation Format: Caterina Ieranò, Crescenzo D'Alterio, Simona Giarra, Maria Napolitano, Assunta Santagata, Antonio Barbieri, Virginia Campani, Antonio Luciano, Claudio Arra, Annamaria Anniciello, Gerardo Botti, Laura Mayol, Giuseppe De Rosa, Roberto Pacelli, Stefania Scala. In vivo capture of early metastatic cells through a CXCL12 loaded-dermal filler [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5194.