ARSB has been studied in a variety of cancers. Cultured normal mammary epithelial and
myoepithelial cells had significantly higher ARSB activity than cultured malignant mammary cells. Immunohistochemistry in the colon showed decreased membrane ARSB staining in
colon cancer compared to normal colon, as well as in higher grade malignancies. ARSB activity was lower in malignant than normal prostate tissue, and immunostaining of prostate tissue microarrays showed not only decreasing ARSB staining in
prostate cancer tissue of a higher
Gleason score, but also lower staining in patients with recurrent compared to non-recurrent cancer. ARSB staining was a greater predictor of recurrence than
Prostate-specific antigen (PSA) test, indicating possible future role of ARSB as a prognostic biomarker of prostate cancer. Further evidence of ARSB as a tumor suppressor was determined by molecular studies in cell cultures where ARSB was silenced by
siRNA. The studies showed that decrease of ARSB leads to increase in free
galectin-3, which attaches more strongly to less sulfated chondroitin 4-sulfate. Galectin-3 then acts on transcription factors
AP-1 to increase expression of chondroitin sulfate
proteoglycan versican and
SP-1 to increase expression of
WNT9A. Another mechanism by which reduced ARSB is associated with carcinogenesis is through increased binding of
SHP2 to more sulfated chondroitin 4-sulfate, which leads to increased phosphorylation of
p38 and
MITF with subsequently increased expression of
GPNMB. == Role in metabolism ==