Extracellular matrix chondroitin/dermatan sulfate proteoglycans are present in a wide variety of tissues including cartilage, placenta, aorta, tendon, brain and skin. They possibly participate in cellular processes such as cell adhesion, migration and proliferation. Recently, we have determined the entire primary structure of the large fibroblast proteoglycan, versican, on the basis of its cDNA sequence. Versican belongs to the family of large aggregating proteoglycans. Other members of the family, which have been characterized in terms of their primary structure, are aggrecan in cartilage and neurocan isolated from brain tissues. Due to the extensive sequence similarities between these three proteoglycans in the N- and C-terminal domains and due to the high degree of carbohydrate substitution, the generation of antibodies monospecific for versican has been difficult. To avoid cross-reactivity with aggrecan and neurocan, we therefore prepared unique portions of versican in a bacterial expression system and used them to immunize rabbits (Zimmermann et al., 1994). The affinity-purified anti-fusion protein antibodies specifically reacted with intact versican from an osteosarcoma cell line. First immunohistochemical experiments on cryo-sections of human skin revealed anti-versican staining in the stratum basale of the epidermis, as well as in the papillary and reticular layers of the dermis. By indirect immunofluorescence, Northern and Western blotting we could demonstrate that both, dermal fibroblasts and keratinocytes express versican in primary cultures. A striking inverse correlation between versican expression and cell density was observed. Analogous to the in vivo situation, keratinocytes induced to terminally differentiate ceased to express versican.(ABSTRACT TRUNCATED AT 250 WORDS)