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Comparison of Growth Factors Functionally Related to Epidermal Growth Factor in the Urine of Normal and Human Tumor-bearing Athymic Mice

Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701 [D. R. T., G. J. T.]; Biological Response Modifiers Program, National Cancer Institute, Frederick, Maryland 21701 [S. A. S., E. S. K.]; and the Frederick Cancer Research Facility, Frederick, Maryland 21701 [J. E. R.]

Urine from nude mice contains epidermal growth factor (EGF) and a minor acid-stable component with an apparent molecular weight of 20,000, which competes with EGF for binding to EGF membrane receptors and which promotes colony formation by normal rat kidney cells in soft agar. The levels of this M_r 20,000 urine-derived growth factor are increased approximately 4- to 10-fold in nude mice bearing tumors following s.c. injection of cultured human tumor cells. Following removal of the primary tumor, the concentration of this factor is reduced to basal levels, and thus, elevated levels of this growth factor appear to be dependent on tumor burden. The M_r 20,000 urinary component is separable into four EGF competing activities by high-performance liquid chromatography; the major species is immunologically related to mouse submaxillary gland EGF and therefore appears to be of host origin.

However, in addition to elevated levels of host growth factor, urine from tumor-bearing mice also contains transforming growth factor activity in amounts comparable to that released by the tumor cells in culture. The tumor-derived urinary transforming growth factor activity is immunologically unrelated to EGF but is immunoreactive with an antiserum to transforming growth factor-. We propose that the nude mouse may be a useful model to examine the role of both host- and tumor-derived growth factors in tumorigenesis and the usefulness of these factors as biological markers of response to therapy and tumor progression.

¹ Present address: Oncogen, 3005 First Avenue, Seattie, WA 98121.

² Present address: Ayerst Laboratories Research, Inc., Department of immunology, CN 8000, Princeton, NJ 08540. To whom requests for reprints should be addressed.

³ Present address: Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080.

Received 6/23/83. Revised 12/ 4/84. Accepted 1/24/85.