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Effect of Inhibitors from Adult Connective Tissue on Growth of a Series of Human Tumors in Vitro¹

( Department of Surgery and Institute of Cancer Research, College of Physicians and Surgeons, Columbia University, New York, New York)

The extraction of growth inhibitors from normal adult connective tissue (aorta, tendon, and muscle) by mild tryptic digestion is described. More than 100 growth inhibitory preparations, including crude tissue extracts, fractions, and subfractions were tested for their effects on growth in primary tissue culture of 25 biopsies of human tumors. The growth of many tumors was reduced 75–100% when incubated in these solutions before being cultured. The preparations were particularly effective against sarcomas, but inhibited the growth of other tumors as well (melanomas, hemangiopericytomas, a xanthoma, and a thymoma); the supporting mesenchymal cells of other tumors were also inhibited. These results appear to support the thesis that a balance of stimulatory and inhibitory substances controls growth normally.

Histochemical studies indicated that these agents are normal components of the intercellular ground substance. They are nondialyzable macromolecules, highly active biologically, since very small amounts (0.05 mg/ml or less) clearly showed the effects described. Nitrogen values indicated at least 50% protein. No deoxyribonucleic acid (DNA) was present but there was approximately 10% ribonucleic acid (RNA). Sensitive chemical tests failed to reveal significant amounts of hexoses or hexosamines. It appears likely that these factors may be part of complexes associated with proteins such as mucopolysaccharide-nucleic acid-protein complexes.

¹ This investigation was supported by Public Health Service research grant CA-04870 from The National Cancer Institute.

Received 6/ 1/64. Revised 11/20/64.

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