Metastasis is an important prognosis factor in
lung cancer, therefore, it is imperative to identify target molecules and elucidate molecular mechanism of
metastasis for developing new
therapeutics and diagnosis methods. We searched for
metastasis-related
proteins by utilizing a novel antibody
proteome technology developed in our laboratory that facilitated efficient screening of useful target
proteins. Two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis identified sixteen
proteins, which were highly expressed in metastatic
lung cancer cells, as
protein candidates. Monoclonal
single-chain variable fragments (scFvs) binding to candidates were isolated from a scFv-displaying phage library by affinity selection. Tissue microarray analysis of scFvs binding to candidates revealed that
oxysterol binding protein-like 5 (OSBPL5) and calumenin (CALU) were expressed at a significantly higher levels in the lung tissues of
metastasis-positive cases than that in the
metastasis-negative cases (OSBPL5; p=0.0156, CALU; p=0.0055). Furthermore, 80% of OSBPL5 and CALU double-positive cases were positive for
lymph node metastasis. Consistent with these observations, overexpression of OSBPL5 and CALU promoted invasiveness of
lung cancer cells. Conversely, knockdown of these
proteins using respective siRNAs reversed the invasiveness of the
lung cancer cells. Moreover, these
proteins were expressed in lung
tumor tissues, but not in normal lung tissues. In conclusion, OSBPL5 and CALU are related to metastatic potential of
lung cancer cells, and they could be useful targets for
cancer diagnosis and also for development of drugs against
metastasis.