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MUC1/KL-6 expression confers an aggressive phenotype upon myeloma cells.

Endo, Shinya; Nishimura, Nao; Kawano, Yawara; Ueno, Niina; Ueno, Shikiko; Tatetsu, Hiro; Komohara, Yoshihiro; Takeya, Motohiro; Hata, Hiroyuki; Mitsuya, Hiroaki; Masao, Matsuoka; Okuno, Yutaka.
Biochem Biophys Res Commun; 507(1-4): 246-252, 2018 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-30420285
The sialic glycoprotein, MUC1, is known to be involved in the pathogenesis of various types of cancers. KL-6 is one of the surface antigens of MUC1 and also a marker of interstitial pneumonitis. A fraction of patients with myeloma (3.9%) have elevated serum KL-6 levels without any evidence of interstitial pneumonitis and their myeloma cells have high MUC1 expression. We established a myeloma cell line designated EMM1 from a patient with multiple myeloma accompanied with elevated serum KL-6. EMM1 cells expressed high levels of MUC1 compared with other myeloma cell lines. Knockdown of MUC1 in EMM1 cells induced cell cycle arrest during S phase and apoptosis, suggesting that the MUC1 expression is involved in accelerated growth of EMM1 cells. RNA-seq analysis suggests that MUC1 expression activates k-ras and TNFα-induced NFκB pathways in EMM1 cells. We injected EMM1 cells subcutaneously into Rag2-/-Jak3-/- Balb/c mice to establish a mouse xenograft model. These mice had aggressive tumor growth that was accompanied by high serum KL-6 levels. In addition, MUC1 knockdown in EMM1 cells led to inhibited tumor growth. These findings demonstrate that MUC1 serves as a potential target for developing drugs for treatment of patients with KL-6+ myeloma, and EMM1 cells and EMM1-engrafted mice are useful tools for the development of such novel agents.
Selo DaSilva