Abstract
Objectives: The high mortality of breast cancer (BC) is associated with the strong metastatic properties of primary breast tumor cells. The present study was conducted in order to clarify the effect of Cosmc on the growth and metastasis of BC cell lines of different molecular types, which may be implicated in the regulation of Tn and T glycans.Methods: BC cell lines with different molecular types were transduced with shRNA targeting Cosmc or, Cosmc overexpression plasmid in order to explore the role of Cosmc in cell proliferation, migration, invasion, and apoptosis. The protein levels of Tn, T, Cosmc, proliferation-related factors (Ki67 and PCNA) and apoptosis-related factors (Bax and Bad) in BC cell lines were determined by Western blot analyses. Finally, the role of Cosmc was substantiated through in vivo experiments.Results: Cosmc was down-regulated in different subtypes of BC cell lines compared with normal control cells. Overexpression of Cosmc suppressed the proliferation, migration, and invasion, yet promoted the apoptosis of BC cells, as reflected by in vitro experiments. Additionally, in vivo tumor xenografts in nude mice showed that ectopic overexpression of Cosmc inhibited the tumor growth of BC cells. Consequently, the levels of proliferation-related factors and Tn antigen were decreased, while those of apoptosis-related factors and T antigen were increased in BC cells. This observation was confirmed in vivo in xenograft tumors.Conclusion: Collectively, up-regulation of Cosmc potentially impedes BC growth and metastasis by modulating the balance between Tn and T glycans.
Highlights
Breast cancer (BC) is the most frequently occurring cancer among women and its incidence worldwide is on the rise [1], due to insufficiencies in early detection, as well as many patients that do reach a metastatic stage end up succumbing to death [2]
The membrane was blocked in 5% bovine serum albumin (BSA) for 1 h and probed with primary rabbit anti-human antibodies against Cosmc, Ki67, proliferating cell nuclear antigen (PCNA; ab152112, 1:1500), Bcl-2-associated X protein (Bax; ab32503, 1:5000), and Bad (Cambridge, MA, U.S.A.) at 4◦C overnight
Four BC cell lines with different molecular types (Luminal type A: MCF-7, Luminal type B: BT474, HER-2 overexpression type: MDA-MB-453, Triple-negative type: MDA-MB-231) were used in order to investigate the effects of differential expression levels of Cosmc on cellular functions, with the protein level of Cosmc in these four cell lines measured by Western blot
Summary
Breast cancer (BC) is the most frequently occurring cancer among women and its incidence worldwide is on the rise [1], due to insufficiencies in early detection, as well as many patients that do reach a metastatic stage end up succumbing to death [2]. The lack of in-time interventions for invasive and metastatic behaviors of BC cells eventually results in invasion and metastasis, which is the final and fatal stage of BC progression [5]. O-glycans include Tn antigen, sialyl-Tn (sTn), and the Thomsen-Friedenreich (TF or T) antigen; aberrant O-glycosylation is often observed on the tumor cell surface and is related to poor prognosis in patients with cancer [7].
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