Function of cancer cell-derived extracellular matrix in tumor progression

Abstract

How to cite this article: Xiong GF, Xu R. Function of cancer cell-derived extracellular matrix in tumor progression. J Cancer Metasta Treat 2016;2:357-64.Extracellular matrix (ECM) is an essential component of the tumor microenvironment. Cancer development and progression are associated with increased ECM deposition and crosslink. The chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and invasion. It is well recognized that stromal cells are a major source of ECM proteins. However, recent studies showed that cancer cells are also an active and important component in ECM remodeling. Cancer cells deposit a significant amount of collagen, fibronectin, and tenascin C (TNC). Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant sites. ECM-related enzymes and chaperone proteins, such as prolyl-4-hydroxylase, lysyl-hydroxylase, lysyl oxidase, and heat shock protein 47, are also highly expressed in cancer cells. Inhibition of these enzymes significantly reduces cancer growth, invasion, and metastasis. These factors suggest that the cancer cell-derived ECM is crucial for cancer progression and metastasis. Therefore, targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment. Key words:Tumor microenvironment, extracellular matrix, cancer progression, metastasis ABSTRACT Article history:

Tumor Microenvironment Heterogeneity: Challenges and Opportunities

“…The extracellular matrix (ECM) is a complex mixture of structural proteins, glycoproteins, and proteoglycans that provide essential physical scaffolds to maintain tissue structure (Xiong and Xu, 2016). The ECM regulates tissue development and homeostasis whereas, dysregulation of ECM functions promote neoplastic progression.…”

“…Furthermore, the ECM represents an abundant source of soluble factors such as growth factors, angiogenic factors, cytokines and chemokines, proangiogenic platelets and bone marrow-derived cells (BMDCs) (Kuznetsov et al, 2012). Thus, the ECM provides a dynamic and complex network for cancer development, progression and metastasis mediated by extensive reorganization of ECM and increasing matrix stiffness (Acerbi et al, 2015; Pickup et al, 2014; Wei et al, 2015; Xiong and Xu, 2016). …”

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

“…ECM proteins, such as collagen and fibronectin, occurs (Pickup, Mouw, & Weaver, 2014;Xiong & Xu, 2016). In tumors, the ECM cross talk with cell surface receptors (e.g., discoidin receptors, syndecans, and mainly integrins) can activate intracellular proliferation, differentiation and survival signaling pathways- Figure 4 (reviewed in detail by P. Lu, Weaver, and Werb, (2012), Pickup et al, (2014), and Xiong and Xu, (2016)). As an example, the increased activation of the integrin signaling pathway (that activates focal adhesion kinase) can prompt the cells proliferation and survival by suppressing the p53induced apoptosis (Frisch, Vuori, Ruoslahti, & Chan-Hui, 1996).…”

Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

“…Thus, several new agents against a variety of targets are being developed, which are believed to regulate cancer malignancy characteristics such as proliferation, therapeutic resistance and metastasis. Because cancer cells have to overcome the ECM barrier before traversing the long route to reach other organs for metastasis, ECM remodeling factors in the tumor microenvironment have gained considerable attention in cancer biology . Among these factors, HAS2, the rate‐limiting enzyme for HA synthesis, is often elevated in various cancers.…”

“…before traversing the long route to reach other organs for metastasis, ECM remodeling factors in the tumor microenvironment have gained considerable attention in cancer biology. [26][27][28] Among these factors, HAS2, the rate-limiting enzyme for HA synthesis, is often elevated in various cancers. However, although its importance is well documented in many cancers, including glioma, breast cancer and squamous cell carcinoma, 18,29,30 its oncogenic role in CRC remains obscure.…”