Unraveling tumor cell‑tumor microenvironment crosstalk through antibody array technologies (Review)

Abstract

The tumor microenvironment (TME) consists of tumor cells, stromal cells, infiltrating immune cells and non‑cellular components such as extracellular matrix, blood vessels and a wide variety of secreted proteins. Evidence shows that beyond supporting tumor growth, the TME also promotes tumor cell proliferation and invasion and contributes to treatment resistance, ultimately affecting patient prognosis. Cell‑to‑cell communication within the TME is driven by secreted proteins such as cytokines, chemokines, growth factors and interferons, which are produced not only by tumor cells but also by various stromal cells and immune cells. These proteins form a complex signaling network that promotes tumor cell proliferation and invasion and enables tumors to evade innate and adaptive immune responses. Antibody arrays are a technology that can simultaneously screen hundreds of secreted proteins in complex biological samples, aiding in the exploration of this complex signaling network. By combining high‑throughput multiplex immunoassays such as antibody arrays with cellular and molecular biology techniques, researchers have uncovered complex regulatory mechanisms of cytokine networks within the TME. The present review summarized recent findings on the communication between tumor cells and the TME, as well as key secreted proteins essential for tumor progression and the development of therapeutic resistance. In addition, it discusses how high‑throughput antibody arrays contribute to our understanding of regulatory networks of secreted proteins in the TME.

Keywords: antibody array; biomarker; crosstalk; cytokine; secretome; signaling pathway; tumor cell; tumor microenvironment.

Figure 1

Overview of the (TME) structure. The complex TME is composed of various cellular and non-cellular components. Tumor cells, stromal cells, and immune cells interact through direct contact or secreted factors, collectively influencing tumor progression. TME, tumor microenvironment; CAF, cancer-associated fibroblast; DC, dendritic cell; ECM, extracellular matrix; NK cell, natural killer cell; Treg, regulatory T cell.

Figure 2

Overview of main protein array platforms. Key features of two types of antibody arrays (left: sandwich-based; middle: label-based) alongside a reverse-phase protein array (right).