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Direct Cloning of Human Neuroblastoma Cells in Soft Agar Culture¹

Department of Medicine, Division of Oncology, University of Texas Health Science Center, at San Antonio, San Antonio, Texas 78284 [D. D. Von H.]; Midwest Children's Cancer Center, Department of Pediatrics, Medical College of Wisconsin, Milwaukee Children's Hospital and The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin 53233 [J. C., A. H.]; Medicine Branch [E. B.], Department of Pathology [C. R.], and Clinical Oncology Program, Division of Cancer Treatment [R. M.], National Cancer Institute, Bethesda, Maryland 20205; Department of Medicine, Section of Hematology/Oncology, Arizona Health Science Center, Tucson, Arizona 85724 [J. M. T.]; and Department of Pediatric Oncology, University of Connecticut, Farmingham, Connecticut 06032 [A. A.]

An in vitro soft agar technique was used in an attempt to culture neuroblastoma cells from 71 bone marrow, 3 lymph node, and 2 solid tumor specimens from 18 patients with neuroblastoma. One-half of each specimen was sent for routine pathology studies and one-half was cultured in the soft agar system. Colonies appeared within 10 days in histologically positive bone marrows. Light microscopy, electron microscopy, catecholamine secretion, and karyology provided evidence that the colonies were composed of neuroblastoma cells. There were 38 instances in which histological study of the specimen demonstrated neuroblastoma cells. The soft agar system showed colony growth in 30 of these samples (79%). There were a total of 38 specimens that were histologically negative for neuroblastoma. Thirty of these 38 specimens showed no growth in the stem cell assay. Eight histologically negative specimens from 6 patients formed colonies in the soft agar system. Five of these 6 patients showed tumor histologically on prior or subsequent marrow examinations. In addition to a significant correlation between histological and soft agar culture results (p < 0.001), there exists a highly significant positive correlation between the number of colonies per plate and the histological status of the specimen (p < 0.005). Serial marrow samples were cultured on 7 patients. There appears to be an association between the number of colonies that develop in the plate and the clinical course and prognosis of the patient. Decreasing plating efficiencies (number of colonies per number of cells plated) correlated with tumor response. Increasing plating efficiencies indicated tumor relapse. A plating efficiency of 0.1% portended a particularly poor prognosis. Neuroblastoma grows well in this soft agar culture system. This excellent growth provides a good model for both clinical and basic science studies of neuroblastoma.

¹ Supported in part by American Cancer Society Research Grant CH162; BRSG Grant 507 BR-05654 awarded by Biomedical Research Support Grant Program, Division of Research Resources, NIH; American Cancer Society Institutional Grant IN-116B; National Cancer Institute Research Grant CA26226; and the MACC fund (Midwest Athletics Against Childhood Cancer).

² To whom requests for reprints should be addressed.

Received 1/21/80. Accepted 7/14/80.