N-methyl-
glycine (
sarcosine) is known to promote metastatic potential in some
cancers; however, its effects on
bladder cancer are unclear. T24 cells derived from invasive
cancer highly expressed GNMT, and S-adenosyl
methionine (SAM) treatment increased
sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive
cancers expressed low GNMT, and SAM treatment did not produce
sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous
tumors, lung
metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary
sarcosine levels was observed to correlate with
tumor weight. Immunostaining of 86 human
bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and
metastasis. Additionally, urinary
sarcosine concentrations increased in cases of muscle invasion. Notably, urinary
sarcosine concentration may serve as a marker for muscle invasion in
bladder cancer; however, further investigation is necessitated.