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IL-10遺伝子導入ヒト肺腺癌細胞株の転移形成能：微小環境条件の違いによる臓器間heterogeneityの存在
三木豊和、藤木富士夫、篠原　勉、曽根三郎（徳島大・医・第三内科）

IL-10 gene transduction into human adenocarcinoma for inhibition of lung metastasis, but for enhancement of liver metastasis in NK-depeleted SCID mice: Toyokazu MIKI, Fujio FUJIKI, Tsutomu SHINOHARA, Saburo SONE (Third Department of Internal Medicine, School of Medicine, University of Tokushima)

IL-10 gene-transduction into cells of breast cancer and melanoma is shown to result in antimetastatic effect on murine lung metastasis models through the NK cell activation and inhibition of angiogenesis. Little is known, however, about the effect on metastases to other organs. This stduy was designed to examine this by using SCID mice in which multiple metastatic foci on liver and kidneys were formed after i.v. injection of human lung adenocarcinoma cell line, PC14. The transfection of PC14 with mouse IL-10 gene gave rise to highly IL-10 producing clone. In NK-intact SCID mice, IL-10 transfectant, PC14/IL10 formed lower number of lung metastatic foci compared with those of parental and mock cells. Interestingly, in NK-depleted SCID mice PC14/IL10 had higher metastatic potential to liver, whereas their metastases to lungs and kidneys were suppressed as compared with parent and mock cells. Although the mechanism of enhancement of liver metastasis is unclear at present, the present findings suggest that metastatic potential of human adenocarcinoma cells capable of producing IL-10 may be regulated differently in the microenviroments of target organs. Thus, immunotherapy using IL-10 gene transduction should be designed carefully by considering the presence of heterogeneity in the microenvironments of organs, especially in lung cancer patients with NK cell deficiency.