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Responses of Bone Marrow -Glutamyltranspeptidase and Alkaline Phosphatase in Vitro to Tumor-elaborated Granulocytopoietic Factors¹

Departments of Pediatrics [O.G., J.F.H., B.K., M.M.] and Pharmacology[O.G.], Mount Sinai School of Medicine of the City University of New York, New York, New York 10029

Evidence has been obtained for the humoral mediation of the recently noted tumor-induced rise of the host bone marrow -glutamyltranspeptidase (GT) and alkaline phosphatase (AP) content in vivo: normal rat bone marrow suspensions, if incubated for 18 hr to 3 days with serum from mammary carcinoma hosts, show 2- to 8-fold elevations (per cell) of the same 2 enzymes. The active substances(s) is in the acid-stable, HCI-ethanol-soluble polypeptide fraction of the mammary carcinoma extract, and of the hosts' blood serum.

The larger the size of the neoplasm, and the faster its growth rate, the greater the effect of the host serum on the GT and AP of the normal bone marrow cells. In host rats in vivo, this response is followed by increases in the number (as well as the GT and AP content) of circulating granulocytes. Therefore, a positive response on the part of these enzymes in the bone marrow suspension was also sought, and found, upon incubation with preparations which enhance granulocyte colony formation in agar cultures (i.e., colony-stimulating factor and serum from endotoxin-treated rats).

The results indicate: (a) that the increase in GT and AP is a necessary prelude to stimulation of granulocyte multiplication by appropriate growth factors; and (b) that measurement of these enzymes in the short-term liquid culture offers a biochemical test for such factors elaborated by cancers or in nonneoplastic conditions.

¹ This study was supported by USPHS Grant CA 25005 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 3/10/83. Accepted 10/24/83.