thromboplastin and Teratoma

The role of host-derived tissue factor (TF) in tumor growth, angiogenesis, and metastasis has hitherto been unclear and was investigated in this study.. 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.. Our study points to an important but context-dependent role of host TF in tumor formation, angiogenesis and therapy.

Topics: Animals; Antineoplastic Agents, Alkylating; Carcinoma, Lewis Lung; Cell Line, Tumor; Cell Survival; Cyclophosphamide; Embryonic Stem Cells; Endothelial Cells; Humans; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, SCID; Neoplasm Metastasis; Neoplastic Stem Cells; Neovascularization, Pathologic; Secretory Vesicles; Teratoma; Thromboplastin; Time Factors

Previous reports suggest that tissue factor (TF) may play an essential role in embryonic vascular development and tumor angiogenesis. To further examine this relationship, the morphology of fully developed TF-deficient embryos and the growth of TF-deficient teratomas and teratocarcinomas were analyzed. In a 129/Sv genetic background, TF null embryos do not survive beyond mid-gestation. In contrast, 14% of 129/Sv x C57BL/6 TF-deficient embryos escape this early mortality and survive to birth. On gross and microscopic inspection, these late gestation, TF-deficient embryos appear normal. The growth and vascularity of TF(+/+), TF(+/-), and TF(-/-) teratomas and teratocarcinomas are indistinguishable. Thus, tumor-derived TF is not required for tumor growth and angiogenesis and the combined data do not support an essential role for TF in embryonic vascular development.

Topics: Animals; Embryonic and Fetal Development; Female; Gene Deletion; Gene Expression Regulation, Developmental; Male; Mice; Mice, Inbred C57BL; Pregnancy; Teratocarcinoma; Teratoma; Testicular Neoplasms; Thromboplastin