In situ detection of tissue factor in vascular endothelial cells: Correlation with the malignant phenotype of human breast disease

Abstract

Expression of tissue factor (TF) in the endothelium has been observed only rarely in human disease and has been thought to be elaborated on the surface of vascular endothelial cells (VECs) in vitro as an artifact of tissue culture. Using monoclonal antibodies and a novel probe for functional TF, we have localized TF to the VECs (and tumor cells) within the tumors of seven patients with invasive breast cancer but not in the VECs (or tumor cells) of benign tumors from ten patients with fibrocystic disease of the breast. The potent procoagulant TF was shown to be a marker of the initiation of angiogenesis in human breast cancer. Further evidence that the TF was the demonstration of a similar distribution of cross-linked fibrin only in the VECs of the malignant tumors. We interpret these data as further support for the concept that tumor cells can activate nearby VECs and regulate blood vessel growth in vivo. Large clinical pathologic studies will be necessary to determine whether TF is a useful marker for the "switch" to the angiogenic phenotype" in human breast disease and/or correlates with the thromboembolic complications of breast cancer.

Induction of interleukin‐1 and subsequent tissue factor expression by anti‐proteinase 3 antibodies in human umbilical vein endothelial cells

“…Whether been difficult to demonstrate (41). Moreover, our results were obtained with HUVEC from neonatal large-vessel cells, whereas vasculitides occur in mature cells of the human adult microvasculature.…”

Mapping of angiogenic markers for targeting of vectors to tumor vascular endothelial cells

“…Other differences involve expression of the receptors tissue factor, a V b 3 and Tie-2 on the vascular endothelial cells of solid tumors but not of normal tissues. [9][10][11][12][13][14][15][16] The kinetics of solid tumor growth has three phases: an initial phase of slow growth, a second phase of more rapid growth and a third phase of slow growth. 7 This growth pattern was shown to fit a mathematical function 7 that was interpreted in terms of variable rates of 'birth' and 'death' of tumor cells between the interior and periphery of the tumor as growth progresses.…”

The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent mouse tissue factor promoter in fibroblasts

“…Although the primary function of TF in the adult is to initiate blood coagulation (reviewed in Edgington et al, 1991), recent studies suggest that TF may contribute to blood vessel maturation in the developing embryo (Bugge et al, 1996;Carmeliet et al, 1996), to maintenance of the placental labyrinth during gestation (Erlich et al, 1999), and to tumor angiogenesis (Contrino et al, 1996). Tissue factor has also been implicated as a determinant of metastatic potential in melanoma cells (Mueller et al, 1992;Bromberg et al, 1995) and expression of TF in the stromal compartment of breast carcinomas has been shown to correlate with progression to invasive cancer (Contrino et al, 1996;Vrana et al, 1996). Thus, it is important to understand how TF gene expression is regulated in both normal and neoplastic cell types.…”