Regulation of tumor growth and metastasis: the role of tumor microenvironment

Abstract

The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body's immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor's surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols.

Keywords: hormones; immune; metastasis; platelets; regulation; stroma; tumor; tumor microenvironment.

Figure 1

The stroma, immune system, platelets (direct and indirect actions) as well as hormones interplay to regulate tumor growth and spread.

Figure 2

Immune regulation of tumor growth with myeloid and lymphoid cells promoting or suppressing tumor growth. Abbreviations: M1, macrophage M1; M2, macrophage M2; MDSC, myeloid-derived-suppressor cells; NK, natural killer cell; TH, T helper; Treg, regulatory T cell; TC, lymphocyte T cytotoxic; B, B cell.

Figure 3

Direct role of platelets in tumor dissemination: 1-Via their P-selectin, platelets interact with both the endothelium and tumor cells helping their extravasations to the vascular compartment. 2-In the vascular compartment, platelets coating tumor cells form platelet-tumor aggregates that shield aberrant tumor MHC-1 from immunesurveillance. Furthermore, platelets may transfer their normal MHC to malignant cells. 3-Platelets also help the microvascular arrest of the platelet-tumor aggregate at distant sites starting the metastatic process. Abbreviations: MHC, major histocompatibility complex; TC, lymphocyte T cytotoxic.

Figure 4

Indirect action of platelets: platelets attracted to the tumor site are activated and, together with PMPs, they provide a rich source of growth factors which, for most of them, support tumor growth, angiogenesis and lymphogenesis. Furthermore, TFG-β interferes with immunesurveillance. Abbreviations: PMP, platelet microparticles; ADP, adenosine diphosphate; IGF-1, insulin growth factor-1; PF4, platelet factor 4 (or CXCL4); VEGF, vascular endothelium growth factor; TGF-β, transforming growth factor-β; NK, natural killer cell; TC, lymphocyte T cytotoxic; Treg, regulatory T cell.