The CXCR4/SDF-1 axis has been studied extensively because of its role in development and hematopoiesis. In acute myeloid leukemia (AML), elevated expression of CXCR4 has been shown to correlate with shortened survival. Hypoxia increases CXCR4 in several tumor models, but the impact of reduced O2 partial pressure (pO2) on expression and biologic function of CXCR4 in AML is unknown. We determined...

BACKGROUND This study investigated the correlations between CXCR4 and VEGF-C expression and lymph node metastasis in non-small cell lung cancer (NSCLC). METHODS Tumor specimens, lymph nodes, and normal lung tissues were obtained from 110 NSCLC patients who underwent complete resection. Quantitative reverse transcription-PCR and immunohistochemistry assays were conducted to evaluate messenger ...

In this study, we have evaluated 11 pancreatic tumor cell lines and tumor cells from surgical samples of patients with pancreatic adenocarcinoma for expression of the chemokine receptor CXCR4. Six of 11 cell lines expressed detectable mRNA of CXCR4, with three cell lines (AsPC1, Capan1, and Hs766T) having substantial amounts of transcripts. Expression was higher in lines derived from metastatic...

Chemokines are peptide mediators involved in normal development, hematopoietic and immune regulation, wound healing, and inflammation. Among the chemokines is CXCL12, which binds principally to its receptor CXCR4 and regulates leukocyte precursor homing to bone marrow and other sites. This role of CXCL12/CXCR4 is "commandeered" by cancer cells to facilitate the spread of CXCR4-bearing tumor cel...

Epithelial ovarian cancer cells express the chemokine receptor, CXCR4, which may be associated with increased survival and metastatic potential, but the regulation of this receptor is not understood. The inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is found in ovarian cancer biopsies and is associated with increased tumor grade. In this report, we show that CXCR4 expression on ...

Abstract Neural stem cells (NSCs) harboring cancer-driving mutations in the subventricular zone (SVZ) have recently been reported as of origin for human GBM. However, pathological role residual tumor-initiating NSCs (tNSCs) SVZ is undetermined recurrent tumors after surgical removal primary tumor. After resection GBM, most recurrences still appear local around cavity (RC). Accordingly, removal,...

It has been shown that p210(BCR-ABL) significantly impairs CXCR4 signaling. We report here that the migratory response to SDF-1 was profoundly altered in blast crisis, whereas chronic-phase CD34(+) cells migrated normally to this chemokine. This migratory defect was associated with a low CXCR4 membrane expression. In vitro STI-571 treatment of CD34(+) cells from patients in blast crisis markedl...

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare congenital immunodeficiency often caused by mutations in the last 10 to 19 C-terminal amino acids of CXCR4. These mutations impair CXCR4 internalization and increase responsiveness to CXCL12. The CXCR4 C-terminal domain (C-tail) also has a binding site for the actin-binding protein filamin A (FLNA); it is not ...

PURPOSE To determine the expression of the chemokine receptors CXCR4 and CCR7 on human uveal melanoma cells and their metastases and the effect of liver-borne factors on the chemotactic responses of uveal melanoma cells. METHODS Four human uveal melanoma cell lines and three cell lines of uveal melanoma metastases were examined by RT-PCR and flow cytometry for their constitutive expression of...

PURPOSE The chemokine receptor CXCR4 is expressed in many different cancers. In malignant brain tumors, CXCR4 signaling has been implicated in tumor growth, survival, and migration, and pharmacologic inhibition of CXCR4 results in decreased tumor growth in preclinical models. To understand how CXCR4 inhibitors may be incorporated into clinical therapy, we examined determinants of responsiveness...