Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.
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.
Laboratory of Glycobiology and Cell Interactions, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Alicja M
AM
Kmiecik
Department of Histology and Embryology, Medical University, Wroclaw, Poland.
Bartosz
B
Pula
Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Environmental and Life Sciences, Wroclaw, Poland.
Jaroslaw
J
Suchanski
Department of Histology and Embryology, Medical University, Wroclaw, Poland.
Mateusz
M
Olbromski
Department of Histology and Embryology, Medical University, Wroclaw, Poland.
Agnieszka
A
Gomulkiewicz
Laboratory of Glycobiology and Cell Interactions, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Tomasz
T
Owczarek
Department of Tumor Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Krakow, Poland.
Anna
A
Kruczak
Department of Tumor Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Krakow, Poland.
Aleksandra
A
Ambicka
Department of Tumor Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Krakow, Poland.
Janusz
J
Rys
Laboratory of Glycobiology and Cell Interactions, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Environmental and Life Sciences, Wroclaw, Poland.
Maciej
M
Ugorski
Department of Histology and Embryology, Medical University, Wroclaw, Poland.
Marzena
M
Podhorska-Okolow
Department of Histology and Embryology, Medical University, Wroclaw, Poland; Department of Physiotherapy, Wroclaw University School of Physical Education, Wroclaw, Poland.
Piotr
P
Dziegiel
D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D000090023:Metallothionein 3; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*
D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D009419:Nerve Tissue Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3