Contribution of Host-Derived Tissue Factor to Tumor Neovascularization Academic Article uri icon

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abstract

  • OBJECTIVE: The role of host-derived tissue factor (TF) in tumor growth, angiogenesis, and metastasis has hitherto been unclear and was investigated in this study. METHODS AND RESULTS: We compared tumor growth, vascularity, and responses to cyclophosphamide (CTX) of tumors in wild-type (wt) mice, or in animals with TF levels reduced by 99% (low-TF mice). Global growth rate of 3 different types of transplantable tumors (LLC, B16F1, and ES teratoma) or metastasis were unchanged in low-TF mice. However, several unexpected tumor/context-specific alterations were observed in these mice, including: (1) reduced tumor blood vessel size in B16F1 tumors; (2) larger spleen size and greater tolerance to CTX toxicity in the LLC model; (3) aborted tumor growth after inoculation of TF-deficient tumor cells (ES TF(-/-)) in low-TF mice. TF-deficient tumor cells grew readily in mice with normal TF levels and attracted exclusively host-related blood vessels (without vasculogenic mimicry). We postulate that this complementarity may result from tumor-vascular transfer of TF-containing microvesicles, as we observed such transfer using human cancer cells (A431) and mouse endothelial cells, both in vitro and in vivo. CONCLUSIONS: Our study points to an important but context-dependent role of host TF in tumor formation, angiogenesis and therapy.

authors

  • Yu, Joanne
  • May, Linda
  • Milsom, Chloe
  • Anderson, G Mark
  • Weitz, Jeffrey
  • Luyendyk, James P
  • Broze, George
  • Mackman, Nigel
  • Rak, Janusz

publication date

  • November 2008

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