Metastasis of a localized cancer is an event that severely undermines the success of cancer treatment and therefore various approaches and methods to the control this event is of great interest to oncologists. Statistics strongly support that the availability of adjuvant therapy to early detection and intervention holds the best promise for complete remission of a cancer. It is widely held that cancer cells exploit various adhesion molecule repertoires used by hematopoietic cells to migrate to different in vivo sites. The present research has documented that a selected group of surface molecules on migrating cancer cells is essential to this migration. Work described in several disclosures has described the identification and modification of different cell surface markers that promote the binding or adhesion of cancer cells to either A) the primary cancer versus B) those surface markers that promote the binding of cancer cells to various carrier cells for delivery of cancer cells to alternative tissues (metastasis). The different specific aspects of this technology that are developed and supported with examples in the patent are the following:
(i) P-selectin (a cell adhesion molecule) binds to chondroitin sulfate (a major P-selectin ligand on breast cancer cell lines) proteoglycans on the surface of breast cancer cells;
(ii) Platelets and endothelial cells that express P-selectin bind to chondroitin sulfate proteoglycans on the surface of breast cancer cells through the P-selectin molecule;
(iii) Specific inhibition of the P-selectin binding to chondroitin sulfate proteoglycans prevents metastasis by blocking tumor cell interaction with platelets or tumor cell interaction with endothelial cells at secondary sites.
Additional work to examine the interaction of cell surface markers and metastatic triggers in breast cancer cells has revealed a network of markers and covalent modifications of these markers by chondroitin sulfate sulfotransferse which dictate the aggressive behavior. For the first time the metastatic marker Melanoma Chondroitin Sulfate Protein (MCSP) has been found in breast cancer cells. These combined studies and the disclosures from them support therapeutic potential and use of directed biologicals, small molecules or siRNA's to block the formation of chondroitin structures that block or severely reduce metastasis. These therapeutic approaches involve the uses of drugs which are involved in covalent modification of gene products or regulate their expression offer unique adjuvant therapies to current medical and surgical approaches to breast cancer. Researchers have recently completed vivo studies that support of these observations.
CIP – (09-06) Chondroitin Sulfate Profile and Their Carriers as Cancer Therapeutic Target – identifies several chondroitin sulfate proteoglycans associated with various cell surface molecules on cancer cells with roles in tumor metastasis that interact with P-selectin.
Reference: Manuscript “The role of glycosaminoglycans as P-selectin ligands in metastasis of a breast cancer cell line”
06-14, 06-14CIP (09-06) (E) Karbassi & Kieber-Emmons