A Complex and Evolutive Character: Two Face Aspects of ECM in Tumor Progression

Abstract

Tumor microenvironment, including extracellular matrix (ECM) and stromal cells, is a key player during tumor development, from initiation, growth and progression to metastasis. During all of these steps, remodeling of matrix components occurs, changing its biochemical and physical properties. The global and basic cancer ECM model is that tumors are surrounded by activated stromal cells, that remodel physiological ECM to evolve into a stiffer and more crosslinked ECM than in normal conditions, thereby increasing invasive capacities of cancer cells. In this review, we show that this too simple model does not consider the complexity, specificity and heterogeneity of each organ and tumor. First, we describe the general ECM in context of cancer. Then, we go through five invasive and most frequent cancers from different origins (breast, liver, pancreas, colon, and skin), and show that each cancer has its own specific matrix, with different stromal cells, ECM components, biochemical properties and activated signaling pathways. Furthermore, in these five cancers, we describe the dual role of tumor ECM: as a protective barrier against tumor cell proliferation and invasion, and as a major player in tumor progression. Indeed, crosstalk between tumor and stromal cells induce changes in matrix organization by remodeling ECM through invadosome formation in order to degrade it, promoting tumor progression and cell invasion. To sum up, in this review, we highlight the specificities of matrix composition in five cancers and the necessity not to consider the ECM as one general and simple entity, but one complex, dynamic and specific entity for each cancer type and subtype.

Bioprinting and Differentiation of Adipose-Derived Stromal Cell Spheroids for a 3D Breast Cancer-Adipose Tissue Model

“…An enhanced deposition of fibronectin and collagen I by cancer-associated adipocytes was previously reported in a murine transwell-based co-culture [ 63 ]. Fibronectin and collagen I are described to be key players in tumor progression, as their overexpression leads to increased matrix stiffness and concomitantly altered biochemical signaling and cell behavior [ 64 ]. Collagen VI has previously been shown to be abundantly expressed and secreted by adipocytes and to be involved in cancer cell–adipocyte heterotypic signaling.…”

Tumor Solid Stress: Assessment with MR Elastography under Compression of Patient-Derived Hepatocellular Carcinomas and Cholangiocarcinomas Xenografted in Mice

“…Because of the low collagen content in the tumors of our study, we had to define a low internal cutoff (1.7%) for substantial fibrosis. MR elastography under compression should be further assessed in tumors with high desmoplasia, including pancreatic and breast cancer [ 37 ].…”

Transcriptomic Profiling of In Vitro Tumor-Stromal Cell Paracrine Crosstalk Identifies Involvement of the Integrin Signaling Pathway in the Pathogenesis of Mesenteric Fibrosis in Human Small Intestinal Neuroendocrine Neoplasms

“…Similarly, we chose to use HEK293 cells as a stromal cell line based on the previous literature on carcinoid-related fibrogenesis that utilized these cells as a fibroblastic cell line ( 17 , 20 ). Secondly, our in vitro model was designed to evaluate paracrine effects, while the mesenteric tumor microenvironment is more complex and includes direct communication between many different cell types, but also the effects of cell adhesion on extracellular matrix, which may be important in the pathophysiology of fibrosis ( 2 , 64 ). Therefore, we opted to validate these in vitro data in a prospective cohort of human Si-NETs which was well characterized and classified ( 23 ).…”