Proteoglycans play a key role in
cancer development and progression by participating in the constitution of a specific fertile tumor microenvironment. As they are largely overexpressed in the malignant stroma,
proteoglycans provide a reservoir of potential new targets for anticancer
therapies, because they can serve to convey toxic payloads in the close proximity of
cancer cells and subsequently destroy them. In this context,
versican, a
proteoglycan largely overexpressed in several solid
cancers, bears the potential to be such an ideal target. As 4 main
versican isoforms have been characterized, we sought to determine which
isoform could represent the best target in human
breast cancer. We used a series of 10 primary
breast cancer lesions that were characterized as overexpressing the
versican protein, when compared with matched normal breast tissues, using shotgun mass spectrometry and immunohistochemistry experiments. Quantitative polymerase chain reaction and western-blotting experiments were used to evaluate
versican isoform expression in
breast cancer/normal tissue pairs for which ARN quality was excellent. All known
isoforms were significantly overexpressed in the malignant lesions, both at the
mRNA and at the
protein levels. In the course of this study, we also identified and cloned a new alternatively spliced
versican isoform, referred to as V4, which was also found to be upregulated in human
breast cancer. This study provides for the first time a comprehensive
mRNA and
protein analysis of
versican isoforms expression in human breast tissues, and offers insights into which therapeutic strategy would be best suited to target
versican in human
breast cancer lesions.