Targeting delivery of lipocalin 2-engineered mesenchymal stem cells to colon cancer in order to inhibit liver metastasis in nude mice.
One of the major obstacles in cancer therapy is the lack of anticancer agent specificity to tumor tissues. The strategy of cell-based therapy is a promising therapeutic option for cancer treatment. The specific tumor-oriented migration of mesenchymal stem cells (MSCs) makes them a useful vehicle to deliver anticancer agents. In this study, we genetically manipulated bone marrow-derived mesenchymal stem cells with their lipocalin 2 (Lcn2) in order to inhibit liver metastasis of colon cancer in nude mice. Lcn2 was successfully overexpressed in transfected MSCs. The PCR results of SRY gene confirmed the presence of MSCs in cancer liver tissue. This study showed that Lcn2-engineered MSCs (MSC-Lcn2) not only inhibited liver metastasis of colon cancer but also downregulated the expression of vascular endothelial growth factor (VEGF) in the liver. Overall, MSCs by innate tropism toward cancer cells can deliver the therapeutic agent, Lcn2, and inhibit cancer metastasis. Hence, it could be a new modality for efficient targeted delivery of anticancer agent to liver metastasis.
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Mozhgan Dehghan
MD
Harati
Fatemeh
F
Amiri
Fatemeh
F
Jaleh
Ahmad
A
Mehdipour
Mitra Dehghan
MD
Harati
Sedigheh
S
Molaee
Marzieh
M
Bahadori
Mohammad Ali
MA
Shokrgozar
Mohammad Ali
MA
Jalili
Mehryar Habibi
MH
Roudkenar
D000209:Acute-Phase Proteins / Q000008:administration & dosage / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000008:administration & dosage / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage / Q000235:genetics*
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins