Expression of interleukin-12 by adipose-derived mesenchymal stem cells for treatment of lung adenocarcinoma.
BACKGROUND
Studies have revealed mesenchymal cells tend to directionally migrate toward tumor cells and inhibit tumor growth. However, there have been rare reports about adipose-derived mesenchymal stem cells (AMSCs), which achieved stable expression of interleukin (IL)-12 to inhibit lung adenocarcinoma cell migration and invasion. We aimed to achieve stable expression of IL-12 in AMSCs through transgenic technology and utilize the paracrine effect of IL-12 to inhibit lung adenocarcinoma cell migration and invasion.


METHODS
Adipose-derived AMSCs were transduced with lentivirus encoding IL-12. IL-12/AMSCs and lung adenocarcinoma A549 cells were co-cultured using a cylinder column to assess cellular attraction, and expression of Ki67 was detected. Dual-chamber transwell experiments were used to assess migration and invasiveness of A549 cells exposed to conditioned media from IL-12/AMSCs.


RESULTS
When A549 cells were co-cultured with lentivirus vectors (LV)-IL-12-green fluorescent protein (GFP)/AMSCs, the intercellular distance was great (346.44 ± 41.07 μm vs. 201.58 ± 27.96 μm vs. 191.45 ± 24.07 μm) (F = 25.414, P < 0.05); the Ki67-positive rate was low (59.13 ± 17.21% vs. 92.31 ± 6.11% vs. 94.25 ± 5.27%) (F = 21.426, P < 0.05). When the lower Transwell chamber contained culture medium from LV-IL-12-GFP/AMSCs, the percentage of the invasive A549 cells was low (31.55 ± 6.21% vs. 70.65 ± 10.46% vs. 68.65 ± 9.50%) (F = 27.494, P < 0.05). The percentages of colonized A549 cells that invaded the culture media of LV-IL-12-GFP/AMSCs were low (4.46 ± 1.21 vs. 10.11 ± 2.07 vs. 9.48 ± 1.4) (F = 23.219, P < 0.05).


CONCLUSIONS
AMSCs could target lung carcinoma and mediate stable expression of IL-12, to play a role in tumor treatment.
Tianjin Medical University General Hospital Tianjin, China.
Xin
X
Li
Tianjin Medical University General Hospital Tianjin, China.
Peng
P
Zhang
Tianjin Medical University General Hospital Tianjin, China.
Xiaozhi
X
Liu
Tianjin Medical University General Hospital Tianjin, China.
Peng
P
Lv
Gene therapy; interleukin-12; lung adenocarcinoma; mesenchymal stem cell