Role of platelets and breast cancer stem cells in metastasis

Abstract

The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells, resistance to chemotherapy and radiotherapy, and tumor regression capacity. In recent years, it has been shown that the presence of breast cancer stem cells is closely associated with the migration and metastatic ability of cancer cells, as well as with their resistance to chemotherapy and radiotherapy. The tumor microenvironment is one of the main molecular factors involved in cancer and metastatic processes development, in this sense it is interesting to study the role of platelets, one of the main communicator cells in the human body which are activated by the signals they receive from the microenvironment and can generate more than one response. Platelets can ingest and release RNA, proteins, cytokines and growth factors. After the platelets interact with the tumor microenvironment, they are called "tumor-educated platelets." Tumor-educated platelets transport material from the tumor microenvironment to sites adjacent to the tumor, thus helping to create microenvironments conducive for the development of primary and metastatic tumors. It has been observed that the clone capable of carrying out the metastatic process is a cancer cell with stem cell characteristics. Cancer stem cells go through a series of processes, including epithelial-mesenchymal transition, intravasation into blood vessels, movement through blood vessels, extravasation at the site of the establishment of a metastatic focus, and site colonization. Tumor-educated platelets support all these processes.

The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

“…Platelet α-granules released after platelet activation carry a large amount of growth factors, such as PDGF, VEGF and TGF-β. In the TME, these growth factors are conducive to tumor proliferation, angiogenesis and invasiveness, thereby promoting tumor progression ( 112 ). At the same time, these factors cooperate with heparanase and matrix metalloproteinases (MMPs) in the TME to further promote tumor-related thrombosis ( 113 ).…”

Platelet Membrane: An Outstanding Factor in Cancer Metastasis

“…(4) Metastatic cells become ready for intravasation into the microvessels generated by angiogenesis in the TME [14], developing the ability to attract and conglomerate platelets around them. Platelets provide metastatic cells with the protection they need to travel without being destroyed by the shear force generated by circulating blood or natural killer (NK) cells [15]. These so-called circulating tumor cells (CTC) can extravasate at a site distant from their point of origin, forming a new metastatic focus with the help of platelets [16].…”

“…Now they are in the focus of several research groups worldwide due to their enormous potential to change our paradigmatic understanding of the development of several diseases. Platelets are currently an important focus of research due to their role in developing cancer, angiogenesis, and metastasis [15]. They have various membrane-bound organelles, including mitochondria, alpha granules, dense granules, and lysosomes, in addition to a complex membranous system, known as the open canalicular system (OCS), which allows for the connection of cytosol (as an external medium) and the dense tubular system (DTS), which stores essential metabolic enzymes [18].…”

“…The platelet membrane has been reported to be densely packed with highly specific surface receptors that finely regulate signal-dependent platelet activation [125,126] and can also adaptively regulate the release of granules for coagulation [127], inflammation [128], atherosclerosis [129], antimicrobial host defense [130], angiogenesis [131], wound repair [42], or metastasis [15,132].…”

Understanding Cervical Cancer through Proteomics

“…Each genotypic and phenotypic change gives way to alterations in the tumor microenvironment and tumor progression [6]. It has been observed that all types of cancer share genetic alterations, especially in the signaling pathways that control cell progression, apoptosis, and cell growth [7,8].…”