The role of the SHAP-HA complex and circulating tumor cells in the breast cancer metastasis

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During cancer progression, Hyaluronan(HA), which is a linear polymer of simply repeated N-acetyl glucosamine-glucuronic acid disaccharide units, assembles an extracellular matrix that is favorable for both motility and proliferation of cancer cells. Serum-derived hyaluronan-associated protein(SHAP), which forms covalent linkages with HA(SHAP-HA complex), stimulates to form tumor microenvironment which is formed by HA.We firstly recognized the accumulation of both HA and SHAP in breast cancer specimen. Marked aggregation of both HA and SHAP was identified in the stroma around the cancer nest by immunohistochemical staining of the fixed specimen. Serum level of SHAP-HA complexes was elevated with the progression of the primary cancer staging. We concluded that SHAP modification of HA may have an important role in tumor proliferation.