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Metastasis is a key factor that limits survival in the majority of patients with cancer. Thus, numerous efforts have been made to elucidate the molecular mechanisms involved in this phenomenon. B16‑F10 melanoma cells have been demonstrated to be highly metastatic to the lungs in mice. The aim of the current study was to investigate the role of CXC motif chemokine receptor 4 (CXCR4) in the metastatic potential of B16‑F10 melanoma cells in mice. In vitro transfection of B16‑F10 tumor cells with CXCR4 short hairpin RNA (shRNA) expressing plasmids (CXCR4 shRNA) significantly reduced the expression levels of CXCR4 mRNA (80%) and protein (68%), compared with the control. In addition, these results demonstrated that pulmonary metastasis was significantly inhibited (85%) in mice inoculated with CXCR4 shRNA‑transfected B16‑F10 melanoma cells. The polycation‑based nanoparticle (jetPEI) was used to investigate the effect of CXCR4 knockdown in vivo on the metastatic potential of B16‑F10 melanoma cells. The number of pulmonary metastatic nodules was significantly reduced (50%) in animals that received a retro‑orbital injection of jetPEI‑CXCR4‑1 shRNA. The current study demonstrated that CXCR4 serves a role in the metastatic potential of B16‑F10 melanoma cells. Currently there is a great interest in the development of antagonists for the therapeutic targeting of CXCR4 expression. Taking the results of the current study and the fact that CXCR4 is highly conserved between humans and mice into account, this experimental model of metastasis with B16‑F10 melanoma cells may aid in the discovery of CXCR4 antagonists with clinical implications.

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Breast cancer represents a complex and heterogeneous disease that comprises distinct disease conditions, histological features, and clinical outcome. Since many years, it has been demonstrated as an association between HER2 amplification and poor prognosis, because its overexpression is associated with an aggressive phenotype of breast tumor cells. A significant proportion of cases have developed resistance to the current therapies available. Consequently, new prognostic markers are urgently needed to identify patients who are at the highest risk for developing metastases. During the past decade, new insights provided valuable knowledge regarding mechanisms underlying the dynamic interplayed between immune cells and tumor progression. It has been shown that the presence of a lymphocytic infiltrate, particularly of regulatory T cells, in cancer tissue, is associated with clinical outcome promoting rather than inhibiting cancer development and progression. It has been also verified that the clinical value of lymphocytic infiltration in breast cancers could be subtype-dependent, including the HER2-enriched subtype. In this context, this work summarizes proposed to discuss the prognostic value of regulatory T cell infiltration in microenvironment of HER2-enriched breast cancer.

The RNA-dependent protein kinase (PKR) is a serine/threonine kinase that is involved in the regulation of important cell processes such as apoptosis, signal transduction, cell proliferation and differentiation. However, the role played by PKR in cancer remains controversial. RNA interference (RNAi) has currently become an important technique in understanding gene function. Previously, we showed that PKR shRNA downregulates PKR expression in B16-F10 melanoma cells and reduces the metastatic potential of these tumor cells. In the present study, we examined the effect of the intratumoral injection of PKR shRNA‑expressing plasmid on the growth of B16-F10 melanoma in mice. The results showed that this treatment significantly reduced tumor growth. Thus, these findings suggested that PKR acts as a tumor suppressor, a finding that is consistent with our previous study on the experimental model of metastasis. Moreover, the results suggested that this effect may be mediated by the transcription factor NF-κB. The present study confirmed the hypothesis that the direct administration of RNAi-based therapeutics in the target tumor is a promising approach for overcoming the obstacles of systemic delivery. The results also suggested that the intratumoral injection of PKR shRNA‑expressing vector is a novel therapeutic approach for human solid tumors such as cutaneous melanoma and breast cancer, since PKR is overexpressed in these tumors.