Absence of tissue factor is characteristic of lymphoid malignancies of both T- and B-cell origin

Abstract

Summary Background Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias. Objectives We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression. Methods We analyzed TF gene (F3) expression in lymphoid (N=114), myeloid (N=49) and solid tumor (N=856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC). Results In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11). Conclusions We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor.

Disseminated intravascular coagulation in non-Hodgkin lymphoma

“…The incidence of DIC in patients with NHL at the time of diagnosis seems to be much lower than those of acute myeloid leukemia (AML) in Japan; according to a survey research, DIC occurs in 32 % of AML except acute promyelocytic leukemia (APL) [6]. Lymphoma cells are known to have few tissue factors (TF), an essential molecule in initiating the extrinsic coagulation cascade and establishing tumor-related thrombophilia in majority of cancers, on its cell surfaces [7]. Nevertheless, dissemination of lymphoma cells to non-lymphoid tissues especially bone marrows seems to make them more susceptible to DIC; there is a 30.9 % chance to develop DIC in this study if lymphoma cells infiltrate to the bone marrow.…”

Microparticle-associated tissue factor activity in dogs with disseminated intravascular coagulation

“…Although TF expression in canine HSA in situ was not clarified, tumor cells-derived TF-MPs might directly contribute to the MP-TF activity in dogs with HSA. On the contrary, several studies of human patients with lymphoma suggest that hypercoagulability in patients with lymphoma is likely not secondary to tumor-derived TF [2,18]. The hypothesis suggested in human lymphoma also seems plausible in dogs with lymphoma.…”

Tissue factor as a new target for CAR-NK cell immunotherapy of triple-negative breast cancer

“…We and our collaborators along with other groups have identified TF as an angiogenesis-specific receptor on VEGF-stimulated angiogenic microvascular endothelial models in vitro as well as in vivo in angiogenic VECs (the inner layer) of the pathological neovasculature of endometriosis, age-related macular degeneration (AMD) and solid cancers, including melanoma 27,28 , lung cancer 29 and breast cancer 29 , and from tumor xenografts in mice and breast cancer tissues from patients 14,16 . In cancer, TF is highly expressed on the cancer cells in many types of solid cancers 14,23,[30][31][32] , acute myeloid and lymphoblastic leukemia (AML and ALL) and sarcoma 23,32 as well as in Hodgkin's lymphoma 33 and multiple myeloma (MM, TF detected in 10 out of 18 patients with MM and 3 MM lines) 34 .…”