tumor-associated macrophage
Macrophages are recruited to tumours by chemotactic factors and provide many trophic functions that promote tumour progression and metastasis.
These tumour-associated macrophages (TAMs) migrate to hypoxic areas within the tumour, where they stimulate angiogenesis by expressing factors such as vascular endothelial growth factor (VEGF), angiopoietin 1 (ANG1) and ANG2, and recruit other haematopoietic cells — mast cells and neutrophils — that can perform similar tasks.
TAMs also promote tumour invasion by producing proteases — such as urokinase-type plasminogen activator (uPA), matrix metalloproteinase 9 (MMP- or MMP99) and cathepsins — that break down the basement membrane and remodel the stromal matrix.
MMP-9 also contributes to angiogenesis. Various growth factors and chemokines — epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) — contribute to the migration of tumour cells towards vessels and provide proliferative and anti-apoptotic signals to these cells.
Macrophages that are attracted to sites of inflammation or tissue breakdown can also initiate or promote tumorigenesis through their synthesis of oestrogens and the generation of mutagens as a by-product of their production of reactive oxygen and nitrogen-oxide radicals.