Human
growth factor receptor-2 (HER2), overexpressed as a result of gene amplification, is detected in 20-40% of patients with breast, ovarian, endometrial, gastric, bladder, prostate, or
lung cancers, correlated to
metastasis of many
tumors, and considered to be a poor prognostic
indicator for these
tumors. However, the data was controversial for HER2 overexpression and the prognosis of
osteosarcoma, which is the most common primary malignant bone
tumor, presents a therapeutic challenge in medical oncology due to its
metastasis and poor response to current treatments. Previously, we reported that the
immunocasp-6 gene fused by a HER2-specific single-chain antibody with domain II of Pseudomonas
exotoxin A (PEA) and the 5' end of the truncated active
caspase-6 could selectively suppress the HER2-positive
tumor growth. In this study, we extend its application. We first confirmed the higher HER2 expression on the surface of metastatic
osteosarcoma SOSP-9607(E10) cells, which then be proved specifically addicted to immunocasp-6-induced cells killing in vitro. Thereafter, the efficacy of
immunocasp-6 was tested in an
osteosarcoma lung
metastasis mouse model using intramuscular (i.m.)
injections of
liposome-encapsulated vectors. Our results showed that the expression of the
immunocasp-6 gene not only significantly prolonged animal's survival, but also greatly inhibited
tumor metastasis. Thereby, our strategy suggests an alternative approach to treating HER2/neu-positive
osteosarcoma.