Vasostatin, a fragment of
calreticulin, was transfected in the BON cell line to evaluate the feasibility of using it for gene therapy in
neuroendocrine tumors.
Vasostatin transfected cells were subcutaneously inoculated in nude mice.
Burkitt lymphoma cell line, CA46, colorectal
adenocarcinoma cell line, SW480, as well as endothelial cells PAE and SVEC4 were used for evaluating the function of
vasostatin. The results demonstrated that
vasostatin transfer caused enhanced malignant behavior of
neuroendocrine tumor cell line, BON. Cell adhesion, spreading and cellular invasion were also enhanced in
vasostatin-expressing BON cells. Tumor suppressor genes including p53, nm23, Rb and
vinculin were down-regulated. Moreover, cell cycle regulatory
protein, p27kip1, and cell differentiation-related
protein kinase, PKR, were also significantly down-regulated. Furthermore, expression of NKG2D
ligands,
MICA and MICB, were down-regulated. Mice implanted with
vasostatin-expressing BON cells showed an earlier and faster
tumor growth compared to wild type. Anti-proliferative effects of
vasostatin could not be proven in other cells except in PAE. These results indicated that
vasostatin does probably not have a
tumor growth inhibitory effect by itself, but rather modulates processes which are necessary for
tumor growth. Therefore, one should be very careful when using
vasostatin as an anti-tumoral agent in clinical trials, at least for
neuroendocrine tumors.