Adenovirus vector-mediated transfer of 9 kDa granulysin induces DNA fragmentation in HuD antigen-expressing small cell lung cancer murine model cells.

Objective: Granulysin is a tumoricidal molecule secreted by cytotoxic T cells (CTL) and natural killer (NK) cells, that induces apoptotic cell death in tumour cells. It has been demonstrated that small cell lung cancer (SCLC) cell lines are susceptible to NK cells and lymphokine activated killer (LAK) cells, and HuD antigen is assumed to be a target molecule on SCLC cells for host cellular immunity.

Methodology: In order to understand the mechanism of sensitivity of SCLC to cellular immunity, we evaluated granulysin-induced apoptosis using mouse adenocarcinoma Colon 26 (Colon 26/HuD) cells transfected with the 9 kDa active form of granulysin using an adenovirus vector as a murine model of SCLC cells.

Results: Adenovirus vector-mediated transfer of 9 kDa granulysin increased DNA fragmentation in Colon 26/HuD cells 2.5-fold and suppressed Colon 26/HuD proliferation by 21% on day 3 (P < 0.05 for each value) compared with the control adenovirus vector transfer. In contrast, adenovirus vector-mediated transfer of 9 kDa granulysin did not increase DNA fragmentation nor suppress the proliferation of Colon 26 parent cells.

Conclusions: The sensitivity of HuD-expressing tumour cells to granulysin is likely to partially explain the susceptibility of SCLC to cell-mediated immunity.