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Developmental Phase-specific Alkaline Phosphatase Isoenzymes of Human Placenta and Their Occurrence in Human Cancer¹

Tufts Cancer Research Center and the Department of Pathology, Tufts University School of Medicine[L. F., H. M., W. H. F.]; Department of Pathology, Harvard Medical School[S. G. D.]; and Boston Hospital for Women, Boston, Massachusetts 02111 [S. G. D.]

² To whom requests for reprints should be addressed, at 136 Harrison Avenue, Boston, Mass. 02111.

Alkaline phosphatase electrophoretic patterns characteristic of three phases in early human trophoblast development are described in this preliminary communication. Phase 1 (6 to 10 weeks) consists entirely of two heat-sensitive, L-homoarginine-inhibited bands, the slower one of which possesses antigenic determinants of liver-bone-type alkaline phosphatase, whereas the fast band lacks any of the known alkaline phosphatase antigenic determinants. Phase 2 pattern (11 to 13 weeks) is that of a mixture of Phase 1 and Phase 3 isozyme components, the latter exhibiting two isozyme bands with the characteristics of term placental alkaline phosphatase. These three patterns of developmental phase-specific placental alkaline phosphatases correspond in order to non-Regan isoenzyme, a mixture of Regan and non-Regan isozymes and Regan isoenzyme in a variety of human cancer tissues. The biochemical profile characteristic of trophoblast developmental Phase 1 alkaline phosphatase is expressed as 78.5% heat-sensitive inhibition (5 min at 65°), 66.3% L-homoarginine inhibition, and 17.3% L-phenylalanine inhibition where n = 12. It is hypothesized that the alkaline phosphatase of human tumor tissues reflects the expression of placental genes corresponding to one or more phases of trophoblastic development.

¹ Supported in part by Grants CA-13332 and CA-12924 from the National Cancer Institute, NIH, USPHS, Bethesda, Md. The support of the Council for Tobacco Research (Grant 935-M) is acknowledged. This paper was presented at the 66th Annual Meeting of the American Association for Cancer Research in San Diego, Calif., May 8 to 11, 1975 (6).

³ Recipient of Cancer Research Award K6-18453 of the National Cancer Institute. Part of this study was carried out at the University of California at Los Angeles during the tenure of a Visiting Professorship of Pathology in the Department of Pathology.

Received 8/25/75. Accepted 3/15/76.

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