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Elevated Soluble Fas (sFas) Levels in Nonhematopoietic Human Malignancy¹

Departments of Surgical Oncology [G. P. M.], Biomathematics [Y. S.], and Immunology [L. B. O-S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095

Fas is a widely expressed membrane-anchored protein that induces apoptosis. Soluble Fas (sFas), generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We have investigated sFas in 104 cancer patients with nonhematopoietic malignancies using a Fas-specific ELISA and immunoprecipitation. Our studies demonstrate an elevated 40-42-kDa sFas species in both patient serum and tumor explants. These observations provide the first evidence that sFas is increased in patients with solid tumors in a manner reflective of disease stage and tumor burden and argue that sFas can be synthesized and released both systemically and locally within the tumor microenvironment.

¹ Supported by United States Public Health Service Grant CA55195 (to L. B. O-S.), American Cancer Society Grant IM-723 (to L. B. O-S.), a Southern Medical Association Research Project grant, a fellowship research grant from the American Cancer Society, Texas Division (to G. P. M.), and The University of Texas M. D. Anderson Cancer Center support core Grant CA16672 from the National Cancer Institute.

² Present address: Department of Colorectal Surgery, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.

³ To whom requests for reprints should be addressed, at The Department of Immunology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 178, Houston, Texas 77030-4095. Phone: (713) 792-8735; Fax: (713) 745-0846; E-mail: laurie owen-schaub@isqm.mda.uth.tmc.edu.

Received 7/ 3/96. Accepted 7/18/96.

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