Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression

Abstract

It has been recently found that metallothionein-3 (MT3) enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001). Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC), nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients’ shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis

“…For example, Wu et al reported that MT1E, one of the metallothioneins, was considered to be important in bladder cancer cell migration and tumour stage [53]. It has been demonstrated that metallthionein-3 induces migration, proliferation, and invasion in triplenegative breast cancer cells via the induction of metalloproteinase expression [54]. Another key molecular mediator of DC-SIGNR in colon cancer cells is MMP9.…”

Association betweenMMP3andTIMP3polymorphisms and risk of osteoarthritis

“…TIMP-3 is TIMP family member that displays unique molecular properties and features. For example, TIMP-3 appears able to induce apoptosis in melanoma cells, retinal pigment epithelial cells, and breast cancer cells [ 26 – 28 ]. TIMP-3 also acts as a local cytokine in bone, regulating bone metabolism by suppressing osteoblast differentiation and inducing osteoblast apoptosis [ 29 , 30 ].…”

Glaucarubulone glucoside from Castela macrophylla suppresses MCF‐7 breast cancer cell growth and attenuates benzo[a]pyrene‐mediated CYP1A gene induction

“…AOX1 hydroxylates heterocycles and oxidizes various aldehydes and participates in a myriad of cellular activities (Terao et al, 2006). GPX1 and SOD3 encode for antioxidant enzymes (Guo et al, 2003), while MT3 is known to enhance invasiveness and tumorigenesis (Kmiecik et al, 2015). Gg likely exhibits pro-oxidant actions in MCF-7 cells via downregulation of AOX-1, GPX1 and SOD3.…”