Systematic study of tissue factor expression in solid tumors

Abstract

Background: Elevated tissue factor (TF) expression, although restricted in normal tissue, has been reported in multiple solid cancers, and expression has been associated with poor prognosis. This manuscript compares TF expression across various solid tumor types via immunohistochemistry in a single study, which has not been performed previously.Aims: To increase insight in the prevalence and cellular localization of TF expression across solid cancer types, we performed a detailed and systematic analysis of TF expression in tumor tissue obtained from patients with ovarian, esophageal, bladder, cervical, endometrial, pancreatic, prostate, colon, breast, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and glioblastoma. The spatial and temporal variation of TF expression was analyzed over time and upon disease progression in patient-matched biopsies taken at different timepoints. In addition, TF expression in patient-matched primary tumor and metastatic lesions was also analyzed.Methods and Results: TF expression was detected via immunohistochemistry (IHC) using a validated TF-specific antibody. TF was expressed in all cancer types tested, with highest prevalence in pancreatic cancer, cervical cancer, colon cancer, glioblastoma, HNSCC, and NSCLC, and lowest in breast cancer. Staining was predominantly membranous in pancreatic, cervical, and HNSCC, and cytoplasmic in glioblastoma and bladder cancer. In general, expression was consistent between biopsies obtained from the same patient over time, although variability was observed for individual patients. NSCLC biopsies of primary tumor and matched lymph node metastases showed no clear difference in TF expression overall, although individual patient changes were observed.

Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study

“…Tissue factor (TF) is expressed in many solid tumors, including cervical cancer. 11 Tisotumab vedotin (TV) is a TF-directed antibody-drug conjugate with a proposed multimodal mechanism of action that includes direct cytotoxicity, bystander effects, antibody-dependent cellular cytotoxicity and phagocytosis, and induction of immunogenic cell death. 12 , 13 TV monotherapy is approved in the United States for the treatment of adults with r/mCC who had disease progression on or after chemotherapy, on the basis of the clinically meaningful objective response rate (ORR) and duration of response (DOR) in the pivotal innovaTV 204/GOG-3023/ENGOT-cx6 study.…”

Calotropis procera: A double edged sword against glioblastoma, inhibiting glioblastoma cell line growth by targeting histone deacetylases (HDAC) and angiogenesis

“…The role of TF in glioblastoma angiogenesis or treatment has yet to be discovered. One study has reported higher TF expression in glioblastoma in tumor biopsies obtained from patients [ 54 ]. It is now well-known that tissue factor, aside from its function as a procoagulant activator, plays a significant role in various tumor-associated mechanisms, including angiogenesis [ 55 ] and also it is suggested that, therapeutics that specifically target transcription factors may have wide clinical applications in tumor treatment [ 56 ].…”

The unfolded protein response links ER stress to cancer-associated thrombosis

“…Knockdown of XBP1 or PERK also decreases UPR-mediated generation of procoagulant EVs (Figure 3). Previous studies have shown that TF is expressed on the surface of many tumors, including pancreatic, non-small cell lung, and gastric cancer (31)(32)(33)(34)(35). This surface TF can be transferred to EVTFs through the formation of microvesicles (84,85).…”

“…While tumor-related mechanisms underlying the propensity for cancer to cause thrombosis are not well understood, the release of EVs expressing tissue factor (TF) has been invoked in both animal studies and clinical observations (25)(26)(27). TF expression is upregulated in many tumor cell lines and tumor biopsies (28)(29)(30)(31)(32)(33)(34)(35). Yet the expression of TF in the tumor itself does not explain thrombosis at distant sites.…”