Contribution of host-derived tissue factor to tumor neovascularization

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

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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 micro vesicles, 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.

Original languageEnglish
Pages (from-to)1975-1981
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2008

Keywords

  • Angiogenesis
  • Cyclophosphamide
  • Microvesicles
  • Tissue factor
  • Tumor

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    Yu, J., May, L., Milsom, C., Anderson, G. M., Weitz, J. I., Luyendyk, J. P., Broze, G., Mackman, N., & Rak, J. (2008). Contribution of host-derived tissue factor to tumor neovascularization. Arteriosclerosis, thrombosis, and vascular biology, 28(11), 1975-1981. https://doi.org/10.1161/ATVBAHA.108.175083