Current progress in the inflammatory background of angiogenesis in gynecological cancers

Abstract

A tumor growth depends on the potency of the tumor to support itself with nutrients and oxygen. The development of a vascular network within the tumor is key to its survival. The permanent contest between the tumor and its host involves tumor cells on one side and an immunological system and tissue stroma on the other. The angiogenesis is not only a specialty of the tumor, but it also depends on this complex multidirectional interaction. The most common gynecological cancers, cervical, endometrial and ovarian carcinoma are good examples for studying this problem. In this review, we aim to show that an inflammatory response against a tumor can be reverted into an undesirable process leading to the development of a vascular network within the tumor and, subsequently, further growth of the tumor and progression of a disease. Therefore, a key for tumor management should be searched within the immunological system, rather than focused on cell cycle and anti-angiogenic treatment only.

Keywords: Angiogenesis; Cancer; Extracellular matrix; Inflammation.

Fig. 1

A complex interaction among inflammatory antitumor cells (TAM M1, TAN N1), their products, tumor surrounding including ECM and inflammatory protumor cells (mast cells, TAM M2, TAN N2). Cytokines, interleukins and growth factors are released in hypoxic environment of tumor from both tumor and immunocompetent cells, leading to angiogenesis and autocrine stimulation of macrophages and neutrophils. Angiogenesis is driven directly by the release of proangiogenic factors like VEGF and bFGF from inflammatory cells and indirectly by degradation of ECM and delivery of entrapped angiogenic chemokines or by stimulation of tumor cells to production of VEGF and other chemokines. Tumor cells produce chemokines that participate in a transformation of M1 and N1 cells to their “bad” analogues, conversely M2 and N2, stimulate mast cells to angiogenic activity and stimulate a specific type of neutrophils (Gr1+) to VEGF-independent angiogenesis. For further explanation see text. TAM M1 tumor-associated macrophages type 1, TAN N1 tumor-associated neutrophils type 1, ECM extracellular matrix, TAM M2 tumor-associated macrophages type 2, TAN N2 tumor-associated neutrophils type 2, MC mast cells. Graphic was made with the use of Affinity Designer