Using two- and three-color immunofluorescence analysis, we examined the expression of CXCR-4 on CD34+ cells in 21 samples obtained from leukapheresis (LP) products of cancer patients who underwent G-CSF-supported cytotoxic chemotherapy.
These results suggest that T140 analogs have potential use for cancer therapy, and that small molecular CXCR4 antagonists could potentially replace neutralizing antibodies as anti-metastatic agents for breast cancer.
CXCR4 was diffusely and homogeneously expressed in 59 cancers, which were further divided into 28 high-expression and 31 low-expression cancers by their staining intensity.
Taken together, these results demonstrate a novel estrogen-mediated paracrine pathway for inducing cancer cell proliferation and suggest that SDF-1 and CXCR4 may represent novel therapeutic targets in ERalpha-positive ovarian and breast tumors.
The CXCR4 promoter is shown to have a 'tumor-on' and 'liver-off' status in vitro and in vivo, and CXCR4 may prove to be a good candidate TSP for cancer gene therapy approaches for melanoma and breast cancers.
In matrigel invasion assays, conditioned media from MCF-7/p1 but not MCF-7/p2 cells increased invasion of cancer cells expressing metastasis-associated genes and CXCR4, the receptor for SDF-1alpha.
The mini-HIV variant that uses CD4 and CXCR4 for cell entry could potentially be used against CXCR4-expressing malignancies such as T-lymphoblastic leukemia/lymphoma, natural killer leukemia, and some myeloid leukemias.
Analysis of cancer samples in different disease stages also suggests that some GPCRs, such as endothelin receptor A, may be involved in early tumor progression and others, such as CXCR4, may play a critical role in tumor invasion and metastasis.
Multivariate analysis of the immunohistochemistry results showed that the expression rate of CCR7 was significantly higher in differentiated than in undifferentiated gastric cancertypes (35.1 vs. 15.3%, p<0.001), and that CXCR4 was expressed at a higher rate in intestinal cancer than in diffuse-type cancer (58.8 vs. 22.3%, p<0.001).
The chemokine receptorCXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies.
Targeting chemokine receptor oligomerization and signal transduction for the treatment of cancer, HIV-1 infections, and other CXCR4 mediated inflammatory conditions warrants further investigation.
GeneChip microarray analysis revealed that a number of genes which regulate cancer invasion and metabolism such as CXCR4, angiopoietin-related protein, pyruvate dehydrogenase kinase 1 (PDK1) are also activated by hypoxia in a HIF-1-dependent manner in Mum2B uveal melanoma cells.
Among others, we speculate that miRNAs may find new roles in the regulation of E-cadherin, integrin alphavbeta3, hypoxia-inducible factor-1alpha, syndecan-1, lysyl oxidase, adamalysin metalloproteinase-17, tissue inhibitors of metalloproteinase-3, c-Met and CXCR-4 that underpin the tissue architectural changes associated with malignancy.
Importantly, the involvement of CXCR4 in cancer metastasis and WHIM syndrome appears to be due to dysregulation of the receptor leading to enhanced signaling.
To evaluate the expression of C-X-C motif chemokine receptor 4 (CXCR4) and its signaling cascades, which were previously identified as a key factor for cancer cell progression and metastasis, in cholangiocarcinoma cell lines.