Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: 'When sweet turns sour'

•Chondroitin sulfate glycosaminoglycans are multifaceted key molecules in ovarian carcinogenesis.•Chondroitin sulfates are potential targets for novel diagnostic and therapeutic modalities.•Chondroitin sulfates may be used as micro-environmental hooks for targeted drug-therapy.

Considering the high mortality of ovarian cancer, novel approaches for diagnostics and therapy are urgently needed. Cancer initiation, progression, and invasion occur in a complex and dynamic microenvironment which depends on the interplay between host cell responses and tumor activity. Chondroitin sulfate (CS), a special highly sulfated sugar, forms an important intermediate player in this respect. Depending on the (micro)structural diversity of chondroitin sulfate chains, various ligands interact with this special group of glycosaminoglycans, making it a key molecule for many physiological and pathological processes, including cancer development.This review focuses on the various functions of chondroitin sulfate in tumor growth, angiogenesis, dissemination and immunosilencing of ovarian cancer. We also shed light on possible future diagnostic and therapeutic modalities for ovarian cancer based on the large variety in chondroitin sulfate microstructure and function. It is concluded that the class of chondroitin sulfate represents an attractive target to interfere with the process of ovarian tumorigenesis.