Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

Abstract

Although platelets and the coagulation factors are components of the blood system, they become part of and contribute to the tumor microenvironment (TME) not only within a solid tumor mass, but also within a hematogenous micrometastasis on its way through the blood stream to the metastatic niche. The latter basically consists of blood-borne cancer cells which are in close association with platelets. At the site of the primary tumor, the blood components reach the TME via leaky blood vessels, whose permeability is increased by tumor-secreted growth factors, by incomplete angiogenic sprouts or by vasculogenic mimicry (VM) vessels. As a consequence, platelets reach the primary tumor via several cell adhesion molecules (CAMs). Moreover, clotting factor VII from the blood associates with tissue factor (TF) that is abundantly expressed on cancer cells. This extrinsic tenase complex turns on the coagulation cascade, which encompasses the activation of thrombin and conversion of soluble fibrinogen into insoluble fibrin. The presence of platelets and their release of growth factors, as well as fibrin deposition changes the TME of a solid tumor mass substantially, thereby promoting tumor progression. Disseminating cancer cells that circulate in the blood stream also recruit platelets, primarily by direct cell-cell interactions via different receptor-counterreceptor pairs and indirectly by fibrin, which bridges the two cell types via different integrin receptors. These tumor cell-platelet aggregates are hematogenous micrometastases, in which platelets and fibrin constitute a particular TME in favor of the cancer cells. Even at the distant site of settlement, the accompanying platelets help the tumor cell to attach and to grow into metastases. Understanding the close liaison of cancer cells with platelets and coagulation factors that change the TME during tumor progression and spreading will help to curb different steps of the metastatic cascade and may help to reduce tumor-induced thrombosis.

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

“…Either way, tumor cells infiltrate the EC layer, thereby causing blood components to leak into the surrounding tissue. Among them are coagulation factors that, similar to wound healing, generate a fibrin-rich ECM [ 412 ]. Even before blood vessel leakage occurs, tumor cells induce the resident cells to change their behavior.…”

Characterization of Platelet Function-Related Gene Predicting Survival and Immunotherapy Efficacy in Gastric Cancer

“…GC is one of most common malignancies of the digestive system. There is increasing evidence that platelets can regulate the TME and promote immune escape and, thus, play an important role in tumor progression and metastasis ( Obermann et al, 2021 ). At present, mechanisms related to PFRG regulation of the immune microenvironment are unclear.…”

A Clinical Prognostic Model Based on Preoperative Hematological and Clinical Parameters Predicts the Progression of Primary WHO Grade II Meningioma

“…An increasing number of studies have indicated that tumorigenesis is closely associated with abnormalities in the coagulation cascade response in the early stage of tumor. The coagulation system is an integral component of the unique vascular microenvironment for tumor proliferation and progress ( 28 , 29 ). FIB and DD, as important factors in the coagulation cascade and fibrinolysis processes, respectively, have been shown to be involved in the invasive process of a variety of malignancies ( 8 , 19 , 30 ).…”