Estrogens produced as a result of intratumoral aromatization has been recently shown to play important roles in proliferation of human
non-small cell lung carcinomas (NSCLC), but the details have remained largely unknown. Therefore, in this study, we evaluated the possible roles of intratumoral
aromatase in NSCLCs as follows: (a) evaluation of intratumoral localization of
aromatase mRNA/
protein in six
lung adenocarcinoma cases using
laser capture microdissection combined with quantitative
reverse transcriptase-PCR and immunohistochemistry; (b) examination of the possible effects of isolated stromal cells from lung
carcinoma tissues on
aromatase mRNA transcript expression in lung
carcinoma cell lines (A549 and LK87) through a coculture system; and (c) screening of
cytokines derived from stromal LK001S and LK002S cells using
cytokine antibody arrays and subsequent evaluation of effects of these
cytokines on
aromatase expression in A549 and LK87. Both
aromatase mRNA and
protein were mainly detected in intratumoral
carcinoma cells but not in stromal cells.
Aromatase expression of A549 and LK87 was upregulated in the presence of LK001S or LK002S cells. Several
cytokines such as
interleukin-6 (IL-6),
oncostatin M, and
tumor necrosis factor-alpha, all known as inducible factors of
aromatase gene, were detected in
conditioned media of LK001S and LK002S cells. Treatment of both
oncostatin M and
IL-6 induced
aromatase gene expression in A549 an LK87, respectively. These results all indicated that intratumoral microenvironments, especially
carcinoma-stromal cell interactions, play a pivotal role in the regulation of intratumoral
estrogen synthesis through
aromatase expression in human
lung adenocarcinomas.