Role of angiogenesis factors in formation of metastatic niches.

Abstract

e15534 Background: A metastatic niche indicates a particular location with a specific cell type, epidermal-mesenchymal transition proteins and diffuse signals that are necessary for the growth of metastases. The purpose of the study was to determine levels of VEGFs, their receptors and TGFβ1 in tissues of gastric cancer (GC) and its metastatic niches: the peritoneum and omentum. Methods: The main group included 21 patients with metastatic GC T3-4аN0-3M1; comparison group – 17 non-cancer patients. Levels of VEGFA, VEGFC, sVEGFR1, sVEGFR3 and TGFβ1 in tissues were determined by standard ELISA methods. Results: Levels of growth factors in GC tissues were higher than in controls: VEGFA in T3-4аN0-3M1 – by 2.7 times, in T3-4аN0-3M0 – by 2.5 times; TGFβ1 in T3-4аN0-3M1 – by 5.6 times, in T3-4аN0-3M0 – by 3.5 times. VEGFA levels in primary gastric tumors were similar in all patients, while TGFβ1 in T3-4аN0-3M1 was 1.6 times (p < 0.05) higher than in T3-4аN0-3M0. VEGFA levels in T3-4аN0-3M1 exceeded control values: in the omentum – by 2.8, in the peritoneum – by 4.2 times. TGFβ1 in the omentum and peritoneum in T3-4аN0-3M1 was increased by 2.5 and 3.1 times respectively, compared to controls. Statistically significant differences in VEGFA and TGFβ1 levels in the omentum and peritoneum in T3-4аN0-3M0 were not found. Conclusions: GC is characterized by equally elevated levels of VEGFA, regardless of the presence or absence of metastases. In the omentum and peritoneum with metastases, high VEGF levels can be considered as one of the primary factors for the formation of signaling pathways between metastatic tumor cells and local non-tumor cells in premetastatic niches. Levels of TGFβ1 in the omentum and peritoneum increase only in patients with metastases, and in GC tissue they are increased to a greater extent than in patients without metastases. Probably, in case of T3-4aN0-3M0, the factor produced by the primary tumor was insufficient for its paracrine induction in the metastatic niche, and scattered cells could not transit from “sleeping” to the active state.