Changes in the Balance between Membrane-Bound and Soluble Forms of CD95 (Fas) during Selection of Tumor Cells in vivo

A. V. Pirogov¹, S. G. Abbasova², N. A. Dyakova¹, N. E. Kushlinsky³, and G. I. Deichman^1*

¹Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoye Shosse 24, Moscow, 115478 Russia; fax: (095) 324-1205; E-mail: antitum@space.ru

²Puschino Branch of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, Puschino, Moscow Region, 142290 Russia

³Institute of Clinical Oncology, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoye Shosse 24, Moscow, 115478 Russia

^* To whom correspondence should be addressed.

Received November 17, 2000; Revision received September 25, 2001

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Studies concerning the expression of the receptor CD95 (Fas) by tumor cells and the role of this protein in apoptosis induced by the effector host cells that bear Fas-ligand are mainly focused on the membrane-bound form of Fas. There are only a few data about the production of the soluble form of Fas by the tumor cells, its role in the interaction with the effector host cells, and the possible changes in the synthesis of this protein during tumor progression. In the present work, three in vitro transformed parental cell lines of different origin and 24 of their variants isolated after a short cycle of natural selection in vivo were studied. It was demonstrated for the first time that: 1) production of the soluble Fas by all selected in vivo variant tumor cell lines increased significantly (2-10-fold) in comparison to the initial (parental) cell lines and did not depend on the origin of the parental lines. At the same time, the expression of the membrane-bound form of Fas decreased considerably; 2) variations of the balance between membrane-bound and soluble forms of Fas in selected in vivo variant cells and the expression of the [H₂O₂^CA + PGE^S]-phenotype by these cells (this phenotype determines one of the essential mechanisms of the protection of a tumor cell in vivo) possibly represent independent secondary changes acquired during tumor progression in vivo.

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KEY WORDS: CD95 (Fas), membrane-bound and soluble isoforms, selection of tumor cells in vivo, bcl-2, Rous sarcoma virus

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