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Stage-specific Expression of SSEA-1-related Antigens in the Developing Lung of Human Embryos and Its Relation to the Distribution of These Antigens in Lung Cancers¹

Department of Clinical Science and Laboratory Medicine, Kyoto University, School of Medicine, Kyoto [M. M., K. Z., R. K.]; Department of Anatomy, Shimane Medical University, Izumo [O. T.]; and Department of Surgery, Shiga Medical University, Ohtsu, Japan [Y. O.]

The localization of three carbohydrate antigens, Le^x, Le^y, and sialylated Le^x-i, which are closely related to stage-specific embryonic antigen 1, in the lung of developing human embryos was investigated using specific monoclonal antibodies. In the 38-day-old embryo, when the primitive lung bud has appeared and developed into two lung sacs, only Le^y antigen was specifically positive in the proliferating cells in the terminal portion of lung bud. In the 50–53-day-old embryos, the future bronchi were actively developing from the bronchial buds. At this stage, the Le^y antigen was maximally expressed and the Le^x antigen appeared in the bud cells. In the lung of the 12-week-old embryo, buds for the future bronchioles were lined by simple cuboidal epithelial cells, which were strongly positive for Le^x antigen, weakly positive for Le^y antigen, and still completely negative for sialylated Le^x-i antigen. Sialylated Le^x-i antigen finally appeared in 18-week-old embryos, in the cells of the terminal buds for the future alveoli. At this stage, the Le^x and Le^y antigens were already beginning to disappear and were only weakly positive in cells of terminal buds. At 20 weeks, only sialylated Le^x-i antigen was weakly detected in the cells in the terminal buds; after 8 months, all three antigens were essentially not detected in the respiratory cells in most of the embryos examined in this study. Formation of bronchial glands was detected at 18 weeks, where the developing gland cells were specifically positive for sialylated Le^x-i antigen. Ciliation of the bronchial epithelial cells started at 12 weeks and propagated thereafter. The ciliation was accompanied by the reappearance of Le^y and Le^x antigen in the epithelial cells. These findings collectively indicated that the three antigens all have a physiological significance as stage-specific developmental antigens of the human lung; those antigens were specifically present in the bud cells at each important step of the morphogenesis of the human lung, such as cells in the lung buds, bronchial buds, and terminal buds for the formation of the alveolus, and cells differentiating into bronchial gland cells. The three antigens gradually disappear in the later stage of development along with the maturation process of the lung. Stage-specific embryonic antigen 1 and related antigens are known to be associated with various human cancers, including lung cancers. We suggest that the expression of these antigens in the lung cancer cells is the result of the retrodifferentiation of the cancer cells to the stages of immature embryonic lung cells.

¹ This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan, and Grants-in-Aid from the Uehara Memorial Foundation, the Japanese Foundation for Multidisciplinary Treatment of Cancer, and the Princess Takamatsu Cancer Research Foundation, to R. K.

² To whom requests for reprints should be addressed, at Department of Laboratory Medicine and Clinical Science, Kyoto University, School of Medicine, Shogoin Kawaharacho 54, Sakyoku, Kyoto 606, Japan.

Received 3/18/88. Revised 7/12/88. Accepted 9/14/88.