Pulmonary
adenocarcinoma is frequently associated with brain
metastasis at some stage during the disease course. Host immunity, particularly T cell immunity, plays an important role in the clinicopathological features of
carcinoma proliferation and
metastasis.
Cytokines and
chemokines are members of a family of small secreted
proteins. The relationships between the
cytokines and
cytokine receptor (R), and between
chemokines and
chemokine R are important determinants of selectivity in local immunity. RCAS1 (receptor-binding
cancer antigen expressed on SiSo cells) and
Fas ligand (FasL) are present in neoplastic cells, induce apoptosis of NK/T cells, and play a role in immune evasion. To investigate differences in host immunity between pulmonary
adenocarcinoma with and without brain
metastasis, we performed gene expression profiling, using
chemokine,
chemokine R,
cytokine and
cytokine R
DNA chips. In addition, to assess the extent of immune evasion, we examined the expression of RCAS and FasL. We studied five cases of pulmonary
adenocarcinoma with brain
metastasis (meta) and five cases without brain
metastasis (non-meta). The brain meta cases exhibited diffuse down-regulated profiles, in comparison with normal non-carcinomatous lungs, which were used as controls. Non-meta cases also displayed diffuse down-regulation, however the degree was variable. Expression of RCAS and FasL was detected in almost all cases, but was stronger in meta than non-meta cases. Our findings suggested that
tumor cells evaded host immunity. In the gene tree analysis, brain meta cases and non-meta cases exhibited distinct clustering. Brain meta cases exhibited significantly lower expression of
interleukin 13 receptor alpha2 (IL-13Ralpha2) than non-meta cases. The reduction of IL-13Ralpha2 expression was confirmed by RT-PCR. Immunohistochemically, non-meta
adenocarcinoma cells frequently expressed IL-13Ralpha2, however, IL-13Ralpha2 expression was rare or weak in
adenocarcinomas with meta. Our results suggested that, in addition to immune evasion, the characteristics of the
adenocarcinoma tumors themselves were important for brain
metastasis. However, our study demonstrated the enormous potential of gene expression profiling in clarifying the pathogenesis of brain
metastasis in pulmonary
adenocarcinoma.