CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells

Sehgal, Anil; Keener, Cassie L.; Boynton, Alton L.; Warrick, Jami; Murphy, Gerald P.

doi:10.1002/(sici)1096-9098(199810)69:2<99::aid-jso10>3.0.co;2-m

Cited by 132 publications

(78 citation statements)

References 21 publications

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“…CXCR4 expression has been shown to be heterogeneous in malignant cells of different origin. It was reported to be markedly decreased in hepatocellular carcinomas [14] and increased in glioblastoma multiforme, breast and uterine cancer as well as Burkitt's lymphoma [15,16]. The expression of CXCR4 was found to be significantly upregulated in malignant renal tissue while the expression of its ligand CXCL12a was markedly reduced compared to normal tissue [17].…”

Section: Discussionmentioning

confidence: 96%

Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis

Wang

Yang

et al. 2009

Clin Exp Metastasis

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The chemokine receptor CXCR4 is involved in the metastasis of many cancers. Recent evidence suggests that CXCR4 may be also involved in the metastasis of renal cell carcinoma. We analyzed the expression of CXCR4 in primary carcinomas, metastatic tissues and normal tissues using immunohistochemistry. We further investigated the migration of renal carcinoma cells in response to stimulation by CXCL12 in vitro. We also studied the subcellular localization of CXCR4 in renal cell carcinoma cells in response to CXCL12 by confocal microscopy. We observed the highest percentage of CXCR4 expression in renal cell carcinoma metastases compared with that in renal cell carcinomas and normal renal tissues. We further found that CXCR4 was localized predominantly in the membrane in primary renal cell carcinomas and predominantly in the cytoplasm in renal cell carcinoma metastases. Moreover, we found that CXCR4 was translocated from the cytoplasmic membrane to the cytoplasm upon stimulation by its ligand CXCL12. Renal cell carcinoma metastasis was associated with higher expression of CXCR4 and interaction of CXCR4 and its ligand CXCL12 resulted in the internalization of CXCR4 from the cytoplasmic membrane. These findings implicate the CXCR4-CXCL12 axis in the metastasis of renal cell carcinoma.

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Section: Discussionmentioning

confidence: 96%

Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis

Wang

Yang

et al. 2009

Clin Exp Metastasis

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“…Moreover, treatment of the glioblastoma cell lines with antibody to CXCR4 or CXCL12 inhibited proliferation, suggesting that CXCR4 gene is required to prevent apoptosis following serum withdrawal [65,66]. Similarly systemic administration of CXCR4 antagonists inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells [67]. In some instances CXCR4 may not be responsible for invasion but rather be critical for the outgrowth of micrometastases [68].…”

Section: The Cxcl12-cxcr4 Axis On Cell Proliferation and Survivalmentioning

confidence: 94%

The pivotal role of CXCL12 (SDF-1)/CXCR4 axis in bone metastasis

Wang

Loberg

Taichman

2006

Cancer Metastasis Rev

222

170

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Tumor cells are known to adapt to and utilize existing physiological mechanisms to promote survival and metastasis. The role of the microenvironment in the establishment of a metastatic lesion has become increasingly important as several factors secreted by stromal cells regulate metastatic pattern in a variety of tumor types. Tumor cells interact with osteoblasts, osteoclasts and bone matrix to form a vicious cycle that is essential for successful metastases. Here we review the current concepts regarding the role of an important chemokine/chemokine receptor (SDF-1 or CXCL12/CXCR4) pathway in tumor development and metastasis. CXCL12 secretion by stromal cells is known to attract cancer cells via stimulation of the CXCR4 receptor that is up regulated by tumor cells. CXCL12/CXCR4 activation regulates the pattern of metastatic spread with organs expressing high levels of CXCL12 developing secondary tumors (i.e., the bone marrow compartment). CXCL12 has a wide range of effects in regards to tumor development but the primary role of CXCL12 appears to be the mobilization of hematopoietic stem cells and the establishment of the cancer stem-like cell niche where high levels of CXCL12 recruit a highly tumorigenic population of tumor cells and promotes cell survival, proliferation, angiogenesis, and metastasis.

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“…Various surveys demonstrated the importance of CXCR4 for the metastasis of kidney cancer [7], acute myeloid leukaemia [8] and prostate cancer, where it is likely to be involved in the ability of this cancer to migrate to the bone marrow [9]. Other studies observed a high expression of CXCR4 in CRC [10], glioblastoma [11], pancreatic cancer [12], non-Hodgkin lymphoma [13] and non-small cell lung cancer, where metastasis could be blocked using neutralizing antibodies against mouse CXCL12 [14]. Moreover, recently CXCR4 has been proposed as a prognostic factor for patients with CRC [15], indicating that CXCR4 expression increases the risk for recurrence and for poor survival [16].…”

Section: Introductionmentioning

confidence: 89%

Changes in CXCL12/CXCR4-chemokine expression during onset of colorectal malignancies

et al. 2010

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Chemokines have been proposed to contribute to tumour growth and metastatic spread of several cancer entities. Here, we examined the relative levels of CXCL12/CXCR4 in resection specimens from patients with different malignant and non-malignant colorectal diseases as well as colorectal liver metastases (CRLM). CXCL12/CXCR4 mRNA and protein expression profiles were assessed by quantitative real-time PCR, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry in resection specimens from patients with ulcerative colitis (UC; n = 15), colorectal adenoma (CRA; n = 15), colorectal adenocarcinoma (CRC; n = 47) and CRLM (n = 16). Corresponding non-affected tissues served as control. In contrast to UC tissues, CXCL12 showed a distinct down-regulation in CRA, CRC and CRLM specimens, whereas the corresponding receptor CXCR4 demonstrated a significant up-regulation in CRC and CRLM related to corresponding non-affected tissues (p < 0.05, respectively). Our results strongly suggest an association between CXCL12/CXCR4 expression and the induction of CRA, CRC and the development of CRLM. Therefore, CXCR4 may be a potential target for specific therapeutic interventions.

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CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells

Cited by 132 publications

References 21 publications

Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis

Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis

The pivotal role of CXCL12 (SDF-1)/CXCR4 axis in bone metastasis

Changes in CXCL12/CXCR4-chemokine expression during onset of colorectal malignancies

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