C4St-1 and Chondroitin Sulfate in Stromal Control of wht Signaling in Breast Cancer.

摘要

Molecules of the tumor microenvironment play a critical role in tumor progression 1-4. The proteoglycan chondroitin sulfate, and chondroitin sulfotransferase genes controlling its sulfation fine structure, has been suggested to play critical roles in many aspects of health and disease 5-10; however, its role in breast cancer progression are not well understood. We investigated a novel chondroitin sulfate-based mechanism of tumor-stromal communication and regulation of the canonical Wnt pathway in breast cancer progression. We hypothesized that elevated expression of the Chondroitin-4- sulfotransferase-1 gene (C4ST-1) in tumor-associated stroma represents a novel control mechanism that could enhance canonical Wnt signaling in breast cancer cells through the establishment of a microenvironment enriched in CS-E, a chondroitin sulfate product of C4ST-1. For this, we wanted to firstly determine the functional significance of stromal C4ST-1 and CS-E on the behavior of, and canonical Wnt signaling in, co-cultured breast cancer cells in vitro. Secondly, we wanted to determine the functional role of stromal C4ST-1 and CS-E on breast cancer progression and canonical Wnt signaling in vivo.