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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.

Glioblastoma is one of the most aggressive tumours with a poor response to treatment and a poor prognosis for patients. One of the proteins expressed in glioblastoma tissue is CHI3L1 (YKL-40), which is upregulated and known for its angiogenesis-supporting and pro-tumour immunomodulatory effects in a variety of cancers. In this paper we present the anti-angiogenic, anti-migratory and immunomodulatory effects of the compound G721-0282, an inhibitor of CHI3L1. The inhibitor-induced changes were investigated using conventional techniques as well as the novel label-free digital holographic tomography (DHT), a quantitative phase imaging technique that allows the reconstruction of the refractive index (RI), which is used as an image contrast for 3D visualisation of living cells. DHT allowed digital staining of individual cells and intercellular structures based only on their specific RI. Quantitative spatially resolved analysis of the RI data shows that the concentration of G721-0282 leads to significant changes in the density of cells and their intracellular structures (in particular the cytoplasm and nucleus), in the volume of lipid droplets and in protein concentrations. Studies in the U-87 MG glioblastoma cell line, THP-1 monocytes differentiated into macrophages, human microvascular endothelial cells (HMEC-1) and in the spheroid model of glioblastoma composed of U-87 MG, HMEC-1 and macrophages suggest that inhibition of CHI3L1 may have potential in the antitumour treatment of glioblastoma. In this paper, we also propose a spheroid model for in vitro studies that mimics this type of tumour.

Background/Aim: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) characterized by malignant proliferation of mature T lymphocytes and primary skin involvement. Recent reports suggest that angiogenesis may play a role in the growth and spread of this malignancy. Cluster of differentiation 31 (CD31) is a protein classified into the Ig-superfamily of cell adhesion molecules, expressed on endothelial cells and majority of hematopoietic non-erythroid cells. The aim of our study was to explore the role of angiogenesis in MF. Materials and Methods: We evaluated the expression of CD31 in relation to clinicopathological data and potential impact on patients' outcome in MF utilizing immunohistochemistry (IHC) and western blot (WB) techniques in 73 and 19 MF and 21 and 4 control samples, respectively. Results: In the IHC study, statistical analysis revealed significantly higher CD31 expression in MF compared to the controls (p<0.0001) with highest expression in advanced stages vs. early ones and controls (p<0.0001 for both). In regard to skin involvement, expression was also elevated in more infiltrative (T3, tumors) and in more extensive (T4, erythroderma) cutaneous lesions compared to less infiltrative and limited skin lesions (T1, T2, patches and/or plaques) (p<0.01 for both). Regarding the extracutaneous spread, higher CD31 expression correlated with nodal involvement (N1-3 vs. N0; p<0.0001). In the WB study, statistical analysis revealed significantly higher CD31 expression only in advanced vs. early stage of MF (p<0.05). In regard to skin involvement, expression was also elevated in T3 and T4 as compared T1+T2 (p=0.08, p<0.05; respectively). Higher CD31 expression correlated with nodal involvement (N1-3 vs. N0; p<0.01). A strong significant correlation between CD31 expression at the protein level analyzed by IHC and WB was noticed (r=0.802, p<0.0001). Moreover, strong positive correlations between IHC expression of CD31 and podoplanin (PDPN; r=0.582, p<0.0001), vascular endothelial growth factor C (VEGFC; r=0.332, p<0.01) and Ki-67 (r=0.330, p<0.01) were disclosed. Conclusion: Expression of CD31 in MF skin biopsies provides new evidence for the role of angiogenesis in the progression of MF. Additionally, the new data revealed prompts for further research on potential use of CD31 as a new marker of the disease advancement, as well as the target of new therapeutic strategies.