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Tumor formation dependent on proteoglycan biosynthesis.
J D Esko1, K S Rostand, J L Weinke
1Department of Biochemistry, School of Medicine, University of Alabama, Birmingham 35294.
Science (New York, N.Y.)
|August 26, 1988
Summary
Proteoglycans are crucial for tumor formation. Chinese hamster ovary cell mutants lacking sufficient proteoglycans, especially heparan sulfate proteoglycans, failed to form tumors in mice, indicating their essential role in cancer development.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Proteoglycans are complex macromolecules with diverse biological functions.
- Their specific roles in tumorigenesis remain incompletely understood.
- Chinese hamster ovary (CHO) cell mutants offer a model to study proteoglycan function.
Purpose of the Study:
- To investigate the role of proteoglycans in tumor formation.
- To determine the specific contribution of heparan sulfate and chondroitin sulfate proteoglycans to tumorigenicity.
Main Methods:
- Measuring the tumorigenicity of proteoglycan-deficient CHO cell mutants in nude mice.
- Subcutaneous injection of 10(7) cells.
- Analysis of tumor formation in mutants with varying levels of proteoglycan synthesis and specific proteoglycan deficiencies.
Main Results:
- Mutants with <15% wild-type proteoglycan synthesis did not form tumors.
- Mutants deficient in heparan sulfate proteoglycan synthesis were non-tumorigenic.
- Mutants with altered chondroitin sulfate proteoglycans remained tumorigenic.
- Co-injection of wild-type and mutant cells resulted in tumors containing both cell types, suggesting wild-type proteoglycans support mutant cell survival.
- Heparan sulfate deficiency-related non-tumorigenicity was dependent on a B cell-mediated host immune response.
Conclusions:
- Proteoglycans, particularly heparan sulfate proteoglycans, are essential for initiating tumor formation.
- Wild-type proteoglycans can facilitate the survival of otherwise non-tumorigenic mutant cells.
- The host immune system, specifically B cell-mediated immunity, plays a role in suppressing tumor formation by heparan sulfate-deficient cells.