Platelet Membrane: An Outstanding Factor in Cancer Metastasis

Abstract

In addition to being biological barriers where the internalization or release of biomolecules is decided, cell membranes are contact structures between the interior and exterior of the cell. Here, the processes of cell signaling mediated by receptors, ions, hormones, cytokines, enzymes, growth factors, extracellular matrix (ECM), and vesicles begin. They triggering several responses from the cell membrane that include rearranging its components according to the immediate needs of the cell, for example, in the membrane of platelets, the formation of filopodia and lamellipodia as a tissue repair response. In cancer, the cancer cells must adapt to the new tumor microenvironment (TME) and acquire capacities in the cell membrane to transform their shape, such as in the case of epithelial-mesenchymal transition (EMT) in the metastatic process. The cancer cells must also attract allies in this challenging process, such as platelets, fibroblasts associated with cancer (CAF), stromal cells, adipocytes, and the extracellular matrix itself, which limits tumor growth. The platelets are enucleated cells with fairly interesting growth factors, proangiogenic factors, cytokines, mRNA, and proteins, which support the development of a tumor microenvironment and support the metastatic process. This review will discuss the different actions that platelet membranes and cancer cell membranes carry out during their relationship in the tumor microenvironment and metastasis.

Keywords: cancer cell membrane; microenvironment; platelet membrane; receptors.

Figure 1

Platelet morphology. The biogenesis of platelets begins in the formation of protrusions in the megakaryocyte known as proplatelets. The biological material that will give rise to the platelet is deposited simultaneously to their formation after the fragmentation of the megakaryocyte proplatelet. Platelets develop a series of distinguishable structural elements that include a delimited plasma membrane; invaginations of the superficial membrane that form the open canicular system (OCS); a network of closed channels of the residual endoplasmic reticulum that forms the dense tubular system (DTS); a spectrin-based membrane backbone; an actin-based cytoskeletal network; a peripheral band of microtubules; and numerous organelles including alpha granules; dense granules; peroxisomes; lysosomes; mitochondria and numerous receptors on the different membranes that exist on the platelet. Created by BioRender.

Figure 2

Composition of the platelet plasma membrane. It is constituted by a phospholipid bilayer in which molecular molecules such as cholesterol, glycolipids, and glycoproteins are embedded. The cellular signalization is on a charge of microdomains formed mainly by raft lipids, cholesterol, glycolipids, and proteins such as integrins, immunoglobulins; adhesive glycoproteins; and receptors P-selectin, flotin-1, glycoprotein 1B (GP1B), P2Y12, and CD40, among others. Created by BioRender.

Figure 3

Contribution of platelets in the development of cancer. Cancer cells lose their cell junctions and travel through blood vessels (extravasation), becoming circulating tumor cells (CTC). Platelets help prevent anoikis, help metastatic cells avoid shear force when they extravasate, and confer molecules of the major histocompatibility complex MHC on the tumor surface to prevent their elimination by the immune system.