**3.1 Role of CS-carrying PGs in tumor progression and metastasis**

Alteration in the production and structure of GAG chains and the functional consequences of such alterations is dependent on the PG carrying the GAG chain. PGs isolated from carcinomas contained 32.2% more CS, 18% less DS, and 30% less HS than PGs of normal breast tissue (Vijayagopal et al., 1998). Chondroitin sulfate proteoglycans (CSPGs) were expressed significantly more often in metastases than in primary tumors of uveal melanoma (Kiewe et al., 2006). We have recently found that CSPGs on breast cancer cells also bind to Pselectin receptors, and interruption of this interaction leads to significant reduction in hematogenous metastasis (Monzavi-Karbassi et al., 2007).

Selectin-mediated binding of tumor cells to platelets, leukocytes, and vascular endothelium may regulate their hematogenous spread in the microvasculature (Krause and Turner, 1999). Among selectin molecules, evidence strongly supports P-selectin involvement in tumor metastasis (Kim et al., 1998; Stevenson et al., 2005). Our data suggest that inhibition of Pselectin interaction with CS-GAGs significantly attenuates hematogenous lung metastasis (Monzavi-Karbassi et al., 2007)**.** We have demonstrated that P-selectin binding to the surface of the aggressive breast cancer cell line MDA-MB-231 and MDA-MET is also CS-dependent, suggesting a role for CSPGs in metastatic behavior of human cancer cells. Because of the role of some of these PGs in signaling and tumor phenotype, we speculate that P-selectin interaction with a particular PG may lead to an exclusive tumor cell activation, and consequently survival in circulation. Here, we review the role of the surface PGs able to present CS-GAGs in malignancy.
