CXCR4 Ligands: The Next Big Hit?

Walenkamp, Annemiek; Lapa, Constantin; Herrmann, Ken; Wester, Hans‐Juergen

doi:10.2967/jnumed.116.186874

Cited by 128 publications

(88 citation statements)

References 87 publications

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“…Previous studies reported that SDF-1 was closely associated with angiogenesis and endothelial cell recruitment [35]. Therefore, EA.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the SDF-1/CXCR4 signaling pathway is of vital importance in mesenchymal stem cell-induced osteogenic differentiation [33], and the upregulation of CXCR4 enhanced engraftment and bone mechanics in osteogenesis imperfecta [34]. Moreover, several studies suggested that SDF-1 is closely associated with angiogenesis, which is essential for osteogenesis [35]. Importantly, the downregulation of SDF-1 achieved by treatment with crude fucoidan extract lowered the vascularization in osteosarcoma [36].…”

Section: Introductionmentioning

confidence: 99%

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Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Yang

Xue

Guan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteonecrosis of the femoral head (ONFH) is a devastating orthopedic disease. Previous studies suggested that stromal-cell-derived factor (SDF)-1 was involved in osteogenesis and angiogenesis. However, whether SDF-1 potentiates the angiogenesis and osteogenesis of bone marrow-derived stromal stem cells (BMSCs) in ONFH is not clear. Methods: BMSCs were transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and SDF-1α, and transgenic efficacy was monitored by immunofluorescence. The expression of SDF-1α, runt-related transcription factor 2 (Runx2, osteocalcin (OCN), and alkaline phosphatase (ALP) at the mRNA level was measured by real-time polymerase chain reactions (RT-PCR). The expression of SDF-1α, Runx2, OCN, and p-Smad1/5 were measured at the protein level by Western blot. Transwell migration assay and tube formation assay were utilized to detect the angiogenesis in vitro, whereas the in vivo angiogenesis was monitored by angiography. Immunohistological staining and micro-CT scanning were conducted to assess the histological changes in morphology. Results: In vitro, SDF-1α overexpression in BMSCs promoted osteogenic differentiation and upregulated the expression of osteogenic-related proteins, such as ALP, Runx2, OCN, and p-Smadl/5. In the methylprednisolone induced ONFH rat model used in our investigation, the overexpression of SDF-1α in BMSCs promoted significantly more bone regeneration and the expression of OCN and Runx2 as compared with the effect of vehicle overexpression. Moreover, the morphology of ONFH was ameliorated after the transplantation of BMSCs with SDF-1α overexpression. Furthermore, SDF-1α overexpression in BMSCs significantly increased osteoblastic angiogenesis as indicated by the increased tube formation ability, CD31 expression, and vessel volume. Conclusion: SDF-1α overexpression in BMSCs promotes bone generation as indicated by osteogenesis and angiogenesis, suggesting SDF-1α may serve as a therapeutic drug target for ONFH treatment.

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“…Previous studies reported that SDF-1 was closely associated with angiogenesis and endothelial cell recruitment [35]. Therefore, EA.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Yang

Xue

Guan

et al. 2018

Cell Physiol Biochem

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“…Chia et al (2018) showed that, whilst CSF-1 played a role in macrophage recruitment, signalling to Cxcr4 was absolutely required for the recruitment of macrophages to the Akt-transformed brain in zebrafish tumour initiation, and that PNC-derived Cxcl12 was the major ligand for this interaction [142]. Cxcr4 signalling has been shown to promote progression of many cancers in mammals including glioblastoma, through both cancer cell autonomous signalling and leukocyte interactions [106,[176][177][178][179][180][181]. However, the pro-tumour effect of Cxcr4 signalling at the preneoplastic stage was macrophage specific [142].…”

Section: Chemokines Recruit Leukocytes To Pncsmentioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Cells

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The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

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“…[20] Several inhibitors or antagonists are already being evaluated in clinical PET and SPECT studies as imaging agents for the expression of the prostate-specific membrane antigen in prostate cancers, [21] the somatostatinr eceptor in neuroendocrine tumors, [22] and the chemokine receptor overexpressed in many types of human cancers. [23] Evidencef rom preclinical and clinical studies suggest that antagonists or inhibitors mayb es uperior to agonists, and are paving the way to as hift towards uch molecules as targeting agentsfor cancer imaging. [24] Our radiolabeling strategy involved at hree-component system constituted by the high affinity CFTR-specific targeting unit CFTR inh -172a, ar adiometal ( 99m Tc using the [ 99m Tc (CO) 3 ] + core), and ab ifunctional chelator (BFC),d esigned to bind to the radiometal and biomolecule.…”

Section: Introductionmentioning

confidence: 99%

Targeting of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein with a Technetium‐99m Imaging Probe

et al. 2018

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Cystic fibrosis (CF) is caused by mutations in the gene that encodes the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to almost total absence of CFTR at the plasma membrane, a defect potentially corrected via drug-based therapies. Herein, we report the first proof-of-principle study of a noninvasive imaging probe able to detect CFTR at the plasma membrane. We radiolabeled the CFTR inhibitor, CFTR -172a, with technetium-99m via a pyrazolyl-diamine chelating unit, yielding a novel Tc(CO) complex. A non-radioactive surrogate showed that the structural modifications introduced in the inhibitor did not affect its activity. The radioactive complex was able to detect plasma membrane CFTR, shown by its significantly higher uptake in wild-type versus mutated cells. Furthermore, assessment of F508del CFTR pharmacological correction in human cells using the radioactive complex revealed differences in corrector versus control uptake, recapitulating the biochemical correction observed for the protein.

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CXCR4 Ligands: The Next Big Hit?

Cited by 128 publications

References 87 publications

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Targeting of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein with a Technetium‐99m Imaging Probe

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