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Tumor Biology

, Volume 37, Issue 6, pp 8425–8435 | Cite as

Human umbilical cord mesenchymal stem cells delivering sTRAIL home to lung cancer mediated by MCP-1/CCR2 axis and exhibit antitumor effects

Original Article

Abstract

Mesenchymal stem cells (MSCs) are believed to be a potential vehicle delivering antitumor agents for their tumor-homing capacity, while the underlying mechanism is yet to be explored. The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) has been suggested as a promising candidate for cancer gene therapy owing to its advantage of selectively inducing apoptosis in cancer cells while sparing normal cells. An isoleucine zipper (ISZ) added to the N-terminal of secretable soluble TRAIL (sTRAIL) can generate the trimeric form of TRAIL (ISZ-sTRAIL) and increase its antitumor potential. However, the inefficient delivery and toxicity are still obstacles for its use. In this study, the migration of human umbilical cord mesenchymal stem cells (HUMSCs) to lung cancer was observed through transwell migration assay and animal bioluminescent imaging both in vitro and in vivo. We found that the homing ability of HUMSCs was suppressed after either knocking down the expression of monocyte chemoattractant protein-1(MCP-1) in lung cancer cells or blocking CCR2 expressed on the surface of HUMSCs, indicating the important role of MCP-1/CCR2 axis in the tropism of HUMSCs to lung cancer. Furthermore, we genetically modified HUMSCs to deliver ISZ-sTRAIL to tumor sites specifically. This targeted therapeutic system exhibited promising apoptotic induction and antitumor potential in a xenograft mouse model without obvious side effects. In conclusion, HUMSCs expressing ISZ-sTRAIL might be an efficient therapeutic approach against lung cancer and MCP-1/CCR2 axis is essential for the tumor tropism of HUMSCs.

Keywords

Mesenchymal stem cell Lung cancer TRAIL MCP-1 CCR2 

Notes

Acknowledgments

This work was supported by grants from the Natural Science Foundation of China (No. 81401887), Tianjin Natural Science Foundation (No. 14JCQNJC11500), Science Foundation of Tianjin Medical University (No. 2012KYM03), and National Basic Research Program of China (973 Program) (No. 2012CB9333004).

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Immunology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Immunology and BiotherapyTianjinChina
  2. 2.Department of BiotherapyTianjin Medical University Cancer Institute and HospitalTianjinChina

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