title: Elimination of breast tumor-associated chondroitin  sulfate promotes metastasis.
abstract: Breast cancer is one of the leading causes of  cancer-related deaths amongst women in the USA. The tumor microenvironment has  been suggested to be an attractive therapeutic target for treatment of cancers.  The glycosaminoglycan chondroitin sulfate, as part of the cellular  microenvironment, consists of long linear chains of repeating disaccharide  units, which are covalently attached to core proteins to form chondroitin  sulfate-proteoglycans. In vitro studies have implicated chondroitin  sulfate in various aspects of carcinogenesis, whereas the in vivo roles  of chondroitin sulfate are less clear. Drastically elevated levels of chondroitin  sulfate have been observed within the stromal compartment of many solid tumors,  including human breast carcinomas, the significance of which is unknown. We  examined the role of tumor-associated chondroitin sulfate in breast cancer  progression. Enzymatic elimination of endogenous chondroitin sulfate by  intra-tumor injections of chondroitinase ABC leads to the development of  secondary tumors and increased lung metastases, while primary orthotopic tumor  growth was not affected. These results establish a metastasis-inhibiting effect  of primary breast tumor-associated chondroitin sulfate, which may open novel  carbohydrate-based therapeutic strategies to combat breast cancer.
authors.affiliation: Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Prinz
authors.forename: C M
authors.initials: CM
authors.lastname: Willis
authors.forename: A
authors.initials: A
authors.lastname: Viloria-Petit
authors.forename: M
authors.initials: M
authors.lastname: Klüppel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000378:metabolism*; D005260:Female; D007267:Injections; D008175:Lung Neoplasms / Q000556:secondary*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology*; D051379:Mice
chemical_list: D002809:Chondroitin Sulfates; D019765:Chondroitin ABC Lyase