ABSTRACT
Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma (HNSCC) mortality. The overexpression of chemokine receptor 4 (CXCR4) in HNSCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4+ tumors in a HNSCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4+ HNSCC cells, achieving a high accumulation in CXCR4+ tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4+ cells in HNSCC. Remarkably, to our knowledge, this is the first study testing targeted protein-only nanoparticles in this cancer type, which may represent a novel treatment approach for HNSCC patients.
ABSTRACT
CXCL12 and its receptor CXCR4 can express in breast cancer,and are regulated by several factors in the genesis and development of breast cancer. Lots of researches have proved that CXCL12 and CXCR4 can be used as new independent prognostic makers of breast cancer.Treatment targeted for CXCR4 can be seen as a new kind of combination therapy,which may provides patients a more ideal treatment.
ABSTRACT
Objective: To investigate the role of protein Hsc73 (heat shock cognate protein 73 000) in renal cell cancer metastasis promoted by SDF-1/CXCR4 axis, so as to determine whether Hsc73 participates in CXCR4 nuclear localization. Methods: Western blotting analysis was used to observe the expression of Hsc73 in A498 cells over-expressing CXCR4. The location of Hsc73 and the interaction of CXCR4 with Hsc73 were investigated in SDF-1-stimulated A498 cells by immunohistochemical staining, Co-IP (Co-Immunoprecipitation) experiment, etc. Results: Hsc73 was up-regulated in A498 cells over-expressing CXCR4. Hsc73 was mainly found in the cytoplasm of A498 cells; after stimulation with SDF-1, some Hsc73 appeared in the nuclei. Hsc73 protein was found in the nuclei of A498 cells after Co-IP with anti-CXCR4 antibody. Conclusion: Hsc73 as a common molecular chaperone participates in the intra-cellular translocation of CXCR4; Hsc73 also plays a key role in the activation of SDF-1/CXCR4 signal pathway and may be involved in the nuclear translocalization of CXCR4.