Contribution of host-derived tissue factor to tumor neovascularization.
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.


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.
Yu
Joanne
J
Henderson Research Centre, McMaster University, Hamilton, ON, Canada.
May
Linda
L
Milsom
Chloe
C
Anderson
G Mark
GM
Weitz
Jeffrey I
JI
Luyendyk
James P
JP
Broze
George
G
Mackman
Nigel
N
Rak
Janusz
J
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003520:Cyclophosphamide / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism; D013724:Teratoma / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013925:Thromboplastin / Q000172:deficiency / Q000378:metabolism*; D013997:Time Factors
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D013925:Thromboplastin
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