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Collagen Synthesis by Short-Term Explants of Pediatric Tumors¹

Division of Hematology-Oncology, Childrens Hospital of Los Angeles, Departments of Pediatrics [Y. A. D., E. B., P. A. J.] and Biochemistry [P. A. J.], University of Southern California School of Medicine, Los Angeles, California 90027

Collagens are a heterogeneous family of structural proteins synthesized by many cultured cells including tumor cells. The synthesis of these proteins by three human tumor types commonly encountered in children [neuroblastoma, rhabdomyosarcoma, and nephroblastoma (Wilms' tumor)] was investigated in short-term cultures of freshly excised tumor explants grown on extracellular matrices.

Analysis of the incorporation of [³H]proline into collagenase-sensitive proteins indicated significant collagen production by several Wilms' tumors and rhabdomyosarcomas, while neuroblastomas did not synthesize this structural protein. All eight Wilms' tumor specimens analyzed secreted type IV procollagen. Interstitial types I and III collagens were also produced by these tumors, but in most cases, the ₁ (I):₂ ratio was much higher than the 2:1 ratio expected for type I collagen, indicating a major change in the control of type I collagen production. Rhabdomyosarcomas were very heterogeneous with regard to collagen secretion and synthesized either a single collagen isotype (type III), several collagens including types I, III, and IV, or no detectable collagen.

Our data represent a first quantitative and qualitative analysis of collagen synthesis by primary tumor cultures and reveal much more heterogeneity in collagen biosynthesis by these tumors than reported previously with established cell lines. They also indicate significant alterations in the expression of type I collagen genes in Wilms' tumors.

¹ This research was supported by Grant CA-29397 from the National Cancer Institute and by a grant from the Kenneth Norris, Jr., Cancer Center, University of Southern California, Los Angeles, CA.

² Recipient of a Junior Clinical Faculty Fellowship of the American Cancer Society. To whom requests for reprints should be addressed.

Received 6/20/84. Accepted 12/ 6/84.