Biological implications of macrophage infiltration in human tumor angiogenesis

Mayumi Ono, Hitoe Torisu, Jun Ichi Fukushi, Akihiko Nishie, Michihiko Kuwano

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)


Tumor angiogenesis is believed to be induced by increased production of angiogenic factors and decreased production of angiogenic inhibitors by cancer cells, vascular endothelial cells, and other stromal cell types. Most solid tumor cells are surrounded by stroma comprising interstitial connective tissue, blood vessels, fibroblastic cells, etc. Interaction between the stroma and malignant cells appears to have a critical role in the development of tumor neovasculature. We focused on macrophages, which demonstrate wide heterogeneity in biological function and have an essential role in tumor angiogenesis. Macrophages are terminally differentiated cells which produce a number of potent angiogenic cytokines and growth factors such as vascular endothelial growth factor, tumor necrosis factor-alpha, interleukin-8, and basic fibroblast growth factor. They also modulate events in the extracellular matrix through the secretion of extracellular matrix-degrading enzymes and -modulating enzymes. Thus macrophages could influence various stages of angiogenesis either positively or negatively. We found a close correlation between increased macrophage index, malignancy, and high vascular grade in malignant melanoma, and present a model for the possible involvement of activated macrophages in neovascularization in human malignant melanoma.

Original languageEnglish
Pages (from-to)S69-S71
JournalCancer Chemotherapy and Pharmacology, Supplement
Publication statusPublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Cancer Research


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