Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: Diffuse down-regulation is associated with immune evasion and brain metastasis

  • Authors:
    • Koichi Ohshima
    • Makoto Hamasaki
    • Yoshifumi Makimoto
    • Satoshi Yoneda
    • Akira Fujii
    • Yasushi Takamatsu
    • Manabu Nakashima
    • Takeshi Watanabe
    • Katunobu Kawahara
    • Masahiro Kikuchi
    • Takayuki Shirakusa
  • View Affiliations

  • Published online on: October 1, 2003     https://doi.org/10.3892/ijo.23.4.965
  • Pages: 965-973
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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 α2 (IL-13Rα2) than non-meta cases. The reduction of IL-13Rα2 expression was confirmed by RT-PCR. Immunohistochemically, non-meta adenocarcinoma cells frequently expressed IL-13Rα2, however, IL-13Rα2 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.

Related Articles

Journal Cover

October 2003
Volume 23 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ohshima K, Hamasaki M, Makimoto Y, Yoneda S, Fujii A, Takamatsu Y, Nakashima M, Watanabe T, Kawahara K, Kikuchi M, Kikuchi M, et al: Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: Diffuse down-regulation is associated with immune evasion and brain metastasis. Int J Oncol 23: 965-973, 2003
APA
Ohshima, K., Hamasaki, M., Makimoto, Y., Yoneda, S., Fujii, A., Takamatsu, Y. ... Shirakusa, T. (2003). Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: Diffuse down-regulation is associated with immune evasion and brain metastasis. International Journal of Oncology, 23, 965-973. https://doi.org/10.3892/ijo.23.4.965
MLA
Ohshima, K., Hamasaki, M., Makimoto, Y., Yoneda, S., Fujii, A., Takamatsu, Y., Nakashima, M., Watanabe, T., Kawahara, K., Kikuchi, M., Shirakusa, T."Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: Diffuse down-regulation is associated with immune evasion and brain metastasis". International Journal of Oncology 23.4 (2003): 965-973.
Chicago
Ohshima, K., Hamasaki, M., Makimoto, Y., Yoneda, S., Fujii, A., Takamatsu, Y., Nakashima, M., Watanabe, T., Kawahara, K., Kikuchi, M., Shirakusa, T."Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: Diffuse down-regulation is associated with immune evasion and brain metastasis". International Journal of Oncology 23, no. 4 (2003): 965-973. https://doi.org/10.3892/ijo.23.4.965