Tumorigenic interplay between macrophages and collagenous matrix in the tumor microenvironment

The tumor microenvironment is a heterogeneous tissue that in addition to tumor cells, contain tumor-associated cell types such as immune cells, fibroblasts, and endothelial cells. Considerably important in the tumor microenvironment is its noncellular component, namely, the extracellular matrix (ECM). In particular, the collagenous matrix is subjected to significant alterations in its composition and structure that create a permissive environment for tumor growth, invasion, and dissemination. Among tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are numerous in the tumor stroma and are locally educated to mediate important biological functions that profoundly affect tumor initiation, growth, and dissemination. While the influence of TAMs and mechanical properties of the collagenous matrix on tumor invasion and progression have been comprehensively investigated individually, their interaction within the complex tumor microenvironment was overlooked. This review summarizes accumulating evidence that indicate the existence of an intricate tumorigenic crosstalk between TAMs and collagenous matrix. A better mechanistic comprehension of this reciprocal interplay may open a novel arena for cancer therapeutics.