To clarify the involvement of
autocrine motility factor (AMF) in the phenotype and
biological profiles of human lung
carcinomas, we analysed
protein and
mRNA expression in a total of 180 cases. Immunohistochemistry revealed positive staining in 67.2%, with the highest frequency in
squamous cell carcinoma (SCC; 90.8%) and the lowest in
small cell carcinoma (SmCC; 27.8%). In SCC, the staining frequency and intensity correlated with the degree of morphological differentiation. Generally, the expression levels in immunoblotting analysis corresponded well with immunohistochemical positivity. However, there was less agreement between
protein and
mRNA levels: in SmCC and
large cell carcinomas (LCCs),
mRNA showed higher, but
protein showed lower expression. Among
non-small cell lung carcinomas (NSCLCs), AMF
protein levels correlated inversely with tumour size, but tumours exhibiting
lymph node metastasis showed higher
mRNA expression. In cultured lung
carcinoma cells which comprised all histological subtypes, AMF was detected in the lysates of all ten cell lines. Secreted AMF
protein was detected in the
conditioned media from six cell lines, most of which were SmCC or LCC. Thus, a particular subset of lung
carcinomas secrete AMF, which may promote cell motility via autocrine stimulation through its cognate receptor and cause the
biological aggressiveness seen in SmCC and LCC. Moreover, treatment by
proteasome inhibitors resulted in increased cellular AMF in five cell lines, suggesting that intracellular AMF levels are regulated by both secretion and
proteasome-dependent degradation. In conclusion, AMF was detected in a major proportion of lung
carcinomas, and may play a part not only in proliferation and/or progression of the tumours, but also, possibly, in the differentiation of SCC. Furthermore, higher
mRNA expression may be related to the high metastatic potential of NSCLC and increased
protein secretion, leading to a more aggressive phenotype, such as the invasiveness of SmCC and LCC.