Ubiquitous Expression of the β - Subunit of H⁺-Transporting ATP Synthase on the Surface of Tumor Cells

Abstract

Tumorigenesis is the result of a complex process marked by alterations in the genetic and functional properties of normal cells. Given the heterogeneous nature of both the induction of neoplasia and the cell types involved, it is not surprising that there is as yet no single universal marker by which tumors could be distinguished from normal cells. Identification of such a marker would not only have a potential diagnostic and therapeutic value but also may provide insight into the neoplastic process itself and immune system interactions with tumors. Our investigations of tumor molecules involved in interactions with cytolytic lymphocytes identified a protein on the surface of all tumors examined that bear structural and immunologic identity with the β subunit of H⁺-transporting ATP synthase (F₁βATPase, E.C. 3.6.1.34)¹. F₁βATPase is found exclusively in mitochondria in normal cells. One of the earliest defense mechanisms against neoplastic cells is provided by a subset of lymphocytes known as natural killer (NK) cells². We found that surface FjβATPase is involved in the effector phase of NK cell mediated lysis of tumors¹. In this article we summarize our data on the tumor surface expression of F₁βATPase and its role in NK cell mediated cytotoxicity.