Methylglyoxal‑derived glycated albumin enhances the stemness potential of invasive ductal carcinoma‑derived breast cancer stem‑like cell line KAIMRC1

Type 2 diabetes mellitus (T2DM) is a risk factor for breast cancer (BC) development and recurrence due to multifactorial mechanisms, including the generation of glycated proteins under hyperglycemic conditions. Emerging evidence indicates that hyperglycemia promotes the formation and expansion of BC stem‑like cells (BCSC), contributing to worse outcomes in patients with T2DM. To support early detection and personalized therapy, there is an urgent need to identify novel biomarkers that specifically target BCSCs in patients with T2DM. The present study examined the effects of glycated albumin (GA) on the cellular functions of KAIMRC1, a naturally immortalized BCSC line derived from invasive ductal carcinoma (IDC), the primary breast carcinoma developed in patients with T2DM. Cells were subjected to in vitro assays, including soft agar colony formation, real‑time monitoring of cell proliferation, motility and invasion through a reconstituted basement membrane using the xCELLigence system and western blotting. A triple‑negative BC cell line was used as a comparator. Aldehyde dehydrogenase (ALDH) activity was quantified using a biochemical assay. As expected, KAIMRC1 cells exhibited high ALDH activity, a characteristic feature of cancer stem‑like cells (CSCs). GA induced dose‑dependent increases in KAIMRC1 cell proliferation, motility, invasion and colony formation and was associated with elevated levels of the oncoprotein phosphorylated‑ERK1/2, the receptor for advanced glycation end products (RAGE) and the stemness‑associated proteins OCT3/4 and vimentin. GA‑treated KAIMRC1 cells showed notable invasive capacity despite slow proliferation, consistent with known metastatic potential of quiescent CSCs. Conversely, unglycated albumin had no detectable biological effects except for an anti‑mitogenic response at high concentration. Bioinformatics analyses showed that vimentin mRNA was upregulated in patients with BC and DM and was associated with a poor prognosis in patients with BC. RAGE neutralization attenuated GA‑induced vimentin upregulation. Altogether, these findings show that GA exerts pro‑tumorigenic effects in IDC‑derived CSCs and upregulates vimentin protein expression via RAGE, highlighting the GA‑RAGE axis as a potential therapeutic target and supporting vimentin as a promising prognostic marker for invasive BC in patients with DM.