Journal ArticleDOI
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
Daniel J. Ceradini,Anita R Kulkarni,Matthew J. Callaghan,Oren M. Tepper,Nicholas Bastidas,Mark E. Kleinman,Jennifer M. Capla,Robert D. Galiano,Jamie P. Levine,Geoffrey C. Gurtner +9 more
TLDR
It is shown that SDF-1 gene expression is regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1) in endothelial cells, resulting in selective in vivo expression of S DF-1 in ischemic tissue in direct proportion to reduced oxygen tension.Abstract:
The trafficking of circulating stem and progenitor cells to areas of tissue damage is poorly understood. The chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12) mediates homing of stem cells to bone marrow by binding to CXCR4 on circulating cells. SDF-1 and CXCR4 are expressed in complementary patterns during embryonic organogenesis and guide primordial stem cells to sites of rapid vascular expansion. However, the regulation of SDF-1 and its physiological role in peripheral tissue repair remain incompletely understood. Here we show that SDF-1 gene expression is regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1) in endothelial cells, resulting in selective in vivo expression of SDF-1 in ischemic tissue in direct proportion to reduced oxygen tension. HIF-1-induced SDF-1 expression increases the adhesion, migration and homing of circulating CXCR4-positive progenitor cells to ischemic tissue. Blockade of SDF-1 in ischemic tissue or CXCR4 on circulating cells prevents progenitor cell recruitment to sites of injury. Discrete regions of hypoxia in the bone marrow compartment also show increased SDF-1 expression and progenitor cell tropism. These data show that the recruitment of CXCR4-positive progenitor cells to regenerating tissues is mediated by hypoxic gradients via HIF-1-induced expression of SDF-1.read more
Citations
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Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion
Akira Orimo,Piyush Gupta,Dennis C. Sgroi,Fernando Arenzana-Seisdedos,Thierry Delaunay,Rizwan Naeem,Vincent J. Carey,Andrea L. Richardson,Robert A. Weinberg +8 more
TL;DR: Using a coimplantation tumor xenograft model, it is demonstrated that carcinoma-associated fibroblasts extracted from human breast carcinomas promote the growth of admixed breast carcinoma cells significantly more than do normal mammaries derived from the same patients.
Journal ArticleDOI
Modes of resistance to anti-angiogenic therapy.
Gabriele Bergers,Douglas Hanahan +1 more
TL;DR: Emerging data support a proposition that two modes of unconventional resistance underlieAngiogenesis inhibitors targeting the vascular endothelial growth factor signalling pathways are affording demonstrable therapeutic efficacy in mouse models of cancer and in an increasing number of human cancers.
Journal ArticleDOI
The biology of fracture healing
TL;DR: The basic biology of fracture healing is summarized, which includes an acute inflammatory response including the production and release of several important molecules, and the recruitment of mesenchymal stem cells in order to generate a primary cartilaginous callus.
Journal ArticleDOI
Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: Potential targets of anti-cancer therapy
TL;DR: Evidence is presented here supporting the view that TAM represent a unique and distinct M2-skewed myeloid population and are a potential target for anti-cancer therapy.
Journal ArticleDOI
Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy
TL;DR: This Review focuses on the main chemokines that are found in the human tumour microenvironment, and elaborate on their patterns of expression, their regulation and their roles in immune cell recruitment and in cancer and stromal cell biology.
References
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Isolation of putative progenitor endothelial cells for angiogenesis.
Takayuki Asahara,Toyoaki Murohara,Alison Sullivan,Marcy Silver,Rien van der Zee,Tong Li,Bernhard Witzenbichler,Gina C. Schatteman,Jeffrey M. Isner +8 more
TL;DR: It is suggested that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarianAngiogenesis.
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Targeting HIF-1 for cancer therapy
TL;DR: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion.
Journal ArticleDOI
Involvement of chemokine receptors in breast cancer metastasis.
Anja Müller,Bernhard Homey,Hortensia Soto,Nianfeng Ge,Daniel Catron,Matthew E. Buchanan,Terri McClanahan,Erin Murphy,Wei Yuan,Stephan N. Wagner,Jose Luis Barrera,Alejandro Mohar,Emma Verastegui,Albert Zlotnik +13 more
TL;DR: It is reported that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases and their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis.
Journal ArticleDOI
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.
Jo A. Forsythe,Bing-Hua Jiang,Narayan V. Iyer,Faton Agani,Sandra W. Leung,Robert D. Koos,Gregg L. Semenza +6 more
TL;DR: HIF-1 is implicate in the activation of VEGF transcription in hypoxic cells and this work demonstrates the involvement of Hif-1 in theactivation of V EGF transcription.
Journal ArticleDOI
Circulating Endothelial Progenitor Cells, Vascular Function, and Cardiovascular Risk
Jonathan Hill,Gloria Zalos,Julian Halcox,William H. Schenke,Myron A. Waclawiw,Arshed A. Quyyumi,Toren Finkel +6 more
TL;DR: A strong correlation between the number of circulating endothelial progenitor cells and the subjects' combined Framingham risk factor score was observed and measurement of flow-mediated brachial-artery reactivity revealed a signifi...