Autologous bone marrow stromal cells genetically engineered to secrete an igf-I receptor decoy prevent the growth of liver metastases.
Liver metastases respond poorly to current therapy and remain a frequent cause of cancer-related mortality. We reported previously that tumor cells expressing a soluble form of the insulin-like growth factor-I receptor (sIGFIR) lost the ability to metastasize to the liver. Here, we sought to develop a novel therapeutic approach for prevention of hepatic metastasis based on sustained in vivo delivery of the soluble receptor by genetically engineered autologous bone marrow stromal cells. We found that when implanted into mice, these cells secreted high plasma levels of sIGFIR and inhibited experimental hepatic metastases of colon and lung carcinoma cells. In hepatic micrometastases, a reduction in intralesional angiogenesis and increased tumor cell apoptosis were observed. The results show that the soluble receptor acted as a decoy to abort insulin-like growth factor-I receptor (IGF-IR) functions during the early stages of metastasis and identify sustained sIGFIR delivery by cell-based vehicles as a potential approach for prevention of hepatic metastasis.
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Ni
N
Wang
Lucia
L
Fallavollita
Long
L
Nguyen
Julia
J
Burnier
Moutih
M
Rafei
Jacques
J
Galipeau
Shoshana
S
Yakar
Pnina
P
Brodt
D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism* / Q000637:transplantation*
D017526:Receptor, IGF Type 1