Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer.
Tumor-associated macrophages (TAMs) produce angiogenic factors and in breast cancer are associated with high vascular grade and poor survival. TAMs preferentially migrate to hypoxic areas within tumors and strongly express hypoxia-inducible factor (HIF)-2 alpha. This study examined whether HIF-2 alp...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Journal article |
Jezik: | English |
Izdano: |
2002
|
_version_ | 1826304234190012416 |
---|---|
author | Leek, R Talks, K Pezzella, F Turley, H Campo, L Brown, N Bicknell, R Taylor, M Gatter, K Harris, A |
author_facet | Leek, R Talks, K Pezzella, F Turley, H Campo, L Brown, N Bicknell, R Taylor, M Gatter, K Harris, A |
author_sort | Leek, R |
collection | OXFORD |
description | Tumor-associated macrophages (TAMs) produce angiogenic factors and in breast cancer are associated with high vascular grade and poor survival. TAMs preferentially migrate to hypoxic areas within tumors and strongly express hypoxia-inducible factor (HIF)-2 alpha. This study examined whether HIF-2 alpha was involved in TAM angiogenic activation by correlating its expression with tumor microvessel density as a marker of angiogenesis, and other tumor variables, in a series of human primary invasive breast carcinomas. A correlation was found between high TAM HIF-2 alpha and high tumor vascularity (P < 0.0001), as well as high tumor grade (P = 0.007). The relation of HIF-2 alpha expression to a recently described oxygen-dependent pathway of angiogenesis was also studied, and an inverse relationship was found between TAM HIF-2 alpha and tumor thymidine phosphorylase expression (P = 0.02). These results suggest that TAM HIF-2 signaling may be a useful target for future antiangiogenic strategies but show that tumors use both oxygen-dependent and oxygen deficiency-regulated pathways for angiogenesis. Thus, combined blockade of pathways and careful assessment of these pathways in trials are necessary. |
first_indexed | 2024-03-07T06:14:41Z |
format | Journal article |
id | oxford-uuid:f0ae9a95-ce31-4a7a-a0d6-80540eaf2e2c |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T06:14:41Z |
publishDate | 2002 |
record_format | dspace |
spelling | oxford-uuid:f0ae9a95-ce31-4a7a-a0d6-80540eaf2e2c2022-03-27T11:50:06ZRelation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f0ae9a95-ce31-4a7a-a0d6-80540eaf2e2cEnglishSymplectic Elements at Oxford2002Leek, RTalks, KPezzella, FTurley, HCampo, LBrown, NBicknell, RTaylor, MGatter, KHarris, ATumor-associated macrophages (TAMs) produce angiogenic factors and in breast cancer are associated with high vascular grade and poor survival. TAMs preferentially migrate to hypoxic areas within tumors and strongly express hypoxia-inducible factor (HIF)-2 alpha. This study examined whether HIF-2 alpha was involved in TAM angiogenic activation by correlating its expression with tumor microvessel density as a marker of angiogenesis, and other tumor variables, in a series of human primary invasive breast carcinomas. A correlation was found between high TAM HIF-2 alpha and high tumor vascularity (P < 0.0001), as well as high tumor grade (P = 0.007). The relation of HIF-2 alpha expression to a recently described oxygen-dependent pathway of angiogenesis was also studied, and an inverse relationship was found between TAM HIF-2 alpha and tumor thymidine phosphorylase expression (P = 0.02). These results suggest that TAM HIF-2 signaling may be a useful target for future antiangiogenic strategies but show that tumors use both oxygen-dependent and oxygen deficiency-regulated pathways for angiogenesis. Thus, combined blockade of pathways and careful assessment of these pathways in trials are necessary. |
spellingShingle | Leek, R Talks, K Pezzella, F Turley, H Campo, L Brown, N Bicknell, R Taylor, M Gatter, K Harris, A Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer. |
title | Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer. |
title_full | Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer. |
title_fullStr | Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer. |
title_full_unstemmed | Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer. |
title_short | Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer. |
title_sort | relation of hypoxia inducible factor 2 alpha hif 2 alpha expression in tumor infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in human breast cancer |
work_keys_str_mv | AT leekr relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT talksk relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT pezzellaf relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT turleyh relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT campol relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT brownn relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT bicknellr relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT taylorm relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT gatterk relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer AT harrisa relationofhypoxiainduciblefactor2alphahif2alphaexpressionintumorinfiltrativemacrophagestotumorangiogenesisandtheoxidativethymidinephosphorylasepathwayinhumanbreastcancer |