We have measured the synthesis of several types of glycosaminoglycans by a line of mouse mammary epithelial cells (C1-S1) established from a hyperplastic nodule outgrowth. These epithelioid cells do not grow readily in vivo. Subconfluent monolayer cultures of C1-S1 cells produced more hyaluronic acid than heparan sulfate, but the opposite was true in confluent cultures. At saturation density in culture, the cell surface glycosaminoglycan of C1-S1 cells was approximately 80% heparan sulfate. For comparison, data are also reported on two related tumorigenic sublines (+SA and -SA) established from a spontaneous tumor in a hyperplastic outgrowth. These cells produced mostly hyaluronic acid even when confluent. Furthermore, the net rate of hyaluronic acid synthesis was higher in the more aggressive tumor cells (+SA). The data are consistent with the interpretation that a hyaluronic acid-rich, heparan sulfate-poor environment is associated with the growth of mammary epithelial cells and conversely that a heparan sulfate-rich environment may restrict growth. The glycosaminoglycan environment may thus contribute to growth modulation in vivo.
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