Tissue factor and cancer stem cells: is there a linkage?

Area of Science:

• Oncology
• Hematology
• Molecular Biology

Background:

• Cancer progression frequently involves the coagulation system, termed cancer coagulopathy.
• Cancer cells and tumor stroma possess procoagulant properties, notably through tissue factor (TF) deregulation, influenced by oncogenes and tumor suppressors.
• Cancer stem cells (CSCs)/tumor-initiating cells (TICs) are crucial for tumor initiation and growth, relying on tumor vasculature for niche support.

Purpose of the Study:

• To investigate the role of the tissue factor (TF)/protease-activated receptor (PAR) system in cancer stem cell (CSC) biology and tumor progression.
• To explore how TF/PAR signaling contributes to CSC niche formation and influences tumor initiation, metastasis, recurrence, and treatment resistance.
• To propose targeting the TF/PAR system as a potential therapeutic strategy against cancer by modulating the CSC compartment.

Main Methods:

• Review and synthesis of existing evidence on cancer coagulopathy, TF expression, and CSC interactions.
• Analysis of oncogenic pathways (EGFR, K-ras, p53, PTEN) influencing TF expression in tumor cells.
• Examination of the TF/PAR system's role as a 'blood sensing' mechanism for cancer cells responding to plasma proteases and microenvironmental cues.

Main Results:

• Deregulation of TF expression is linked to oncogenic mutations and is observed in CSCs.
• The TF/PAR system acts as a signaling nexus, mediating interactions between CSCs and their vascular niche.
• Evidence suggests TF/PAR signaling influences CSC-driven tumor initiation, metastasis, recurrence, and therapeutic resistance.

Conclusions:

• The TF/PAR system plays a significant role in supporting the CSC niche and driving cancer progression.
• Targeting the TF/PAR system presents a novel therapeutic avenue for controlling cancer by affecting the CSC compartment.
• Further research into tumor cell- and host-derived TF is warranted to fully exploit this therapeutic opportunity.