CXCR4 and cancer

Furusato, Bungo; Mohamed, Ahmed; Uhlén, Mathias; Rhim, Johng S.

doi:10.1111/j.1440-1827.2010.02548.x

Cited by 254 publications

(213 citation statements)

References 133 publications

(87 reference statements)

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“…126 VEGF is a well-known angiogenic factor that is induced by hypoxia; its complete absence causes embryonic lethality because of a failure to establish angiogenesis as well as hematopoiesis. In addition, as noted earlier, SDF-1 binds to the G-protein-coupled receptor CXCR4 on the surface of some tumor cells (reviewed in Furusato et al 27 ), potentially promoting trafficking and metastasis of CXCR4þ cancer stem cells to organs expressing high levels of SDF-1, such as lymph nodes, lung, and bone. HSCs and HPCs expressing surface CXCR4 may traffic to the SDF-1-producing site in concert with tumor cells, leading to EMH within tumors.…”

Section: Emh Within Neoplasmsmentioning

confidence: 99%

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

2012

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Extramedullary hematopoiesis (EMH) is the formation and development of blood cells outside the medullary spaces of the bone marrow. Although widely considered an epiphenomenon, secondary to underlying primary disease and lacking serious clinical or diagnostic implications, the presence of EMH is far from incidental on a molecular basis; rather, it reflects a well-choreographed suite of changes involving stem cells and their microenvironment (the stem cell niche). The goals of this review are to reconsider the molecular basis of EMH based on current knowledge of stem cell niches and to examine its role in the pathophysiologic mechanisms of EMH in animals. The ability of blood cells to home, proliferate, and mature in extramedullary tissues of adult animals reflects embryonic patterns of hematopoiesis and establishment or reactivation of a stem cell niche. This involves pathophysiologic alterations in hematopoietic stem cells, extracellular matrix, stromal cells, and local and systemic chemokines. Four major theories involving changes in stem cells and/or their microenvironment can explain the development of most occurrences of EMH: (1) severe bone marrow failure; (2) myelostimulation; (3) tissue inflammation, injury, and repair; and (4) abnormal chemokine production. EMH has also been reported within many types of neoplasms. Understanding the concepts and factors involved in stem cell niches enhances our understanding of the occurrence of EMH in animals and its relationship to underlying disease. In turn, a better understanding of the prevalence and distribution of EMH in animals and its molecular basis could further inform our understanding of the hematopoietic stem cell niche.

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Section: Emh Within Neoplasmsmentioning

confidence: 99%

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

2012

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“…Of note, CXCR4 expression and phosphorylation has been considered a negative prognostic marker in various types of cancer including acute myelogenous leukemia and B-acute lymphoblastic leukemia, breast and colon carcinomas, as it correlated with worse prognosis and decreased survival of patients [86,[89][90][91][92] . Increased levels of VEGF, the activation of nuclear factor kappa B (NF-ĸB) and some oncoproteins up-regulate CXCR4 expression, in particular during cancer progression [93,94] and under hypoxic conditions [95] . CXCR4/ SDF-1 contributes to tumor progression also through the activation of tumor-associated integrin and the production of matrix metalloproteases [93] , as observed in human basal carcinoma cells [96] and oral squamous cell carcinomas [97] .…”

Section: Gpcrs Activated By Chemokinesmentioning

confidence: 99%

“…Increased levels of VEGF, the activation of nuclear factor kappa B (NF-ĸB) and some oncoproteins up-regulate CXCR4 expression, in particular during cancer progression [93,94] and under hypoxic conditions [95] . CXCR4/ SDF-1 contributes to tumor progression also through the activation of tumor-associated integrin and the production of matrix metalloproteases [93] , as observed in human basal carcinoma cells [96] and oral squamous cell carcinomas [97] . Recently, CXCR7/RDC1 has been identified as a novel receptor for CXCL12/SDF-1 and CXCL11 [98] , although its coupling to G-proteins remains controversial.…”

Section: Gpcrs Activated By Chemokinesmentioning

confidence: 99%

GPCRs and cancer

Lappano

2012

Acta Pharmacol Sin

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G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients.

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“…Cancer stem cells also express CXCR4, which implies that this axis may control the trafficking and metastasis of these cells to organs that express CXCL12, and the liver is one of these [142] . Recently, Li et al [143] reported that the expression of CXCR4 was higher in portal vein tumor thrombus tissue than hepatocellular carcinoma (HCC), and lentivirus-mediated siRNA knockdown of CXCR4 was shown to impair the potential invasiveness of tumor thrombus cells significantly.…”

Section: Livermentioning

confidence: 99%

“…Marker for late stage gastric cancer [137] Other candidates CC-chemokines (CCL2, 3, 5, 21, 25)/CXC-chemokines (1,7,8,12,14)/CCR6 [139] Liver CXCR4 Metastasis, upregulation in PVTT [142][143] …”

Section: Cxcl5mentioning

confidence: 99%

Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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CXCR4 and cancer

Cited by 254 publications

References 133 publications

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

GPCRs and cancer

Chemokines, chemokine receptors and the gastrointestinal system

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