Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer

Abstract

Extracellular matrix (ECM) plays a pivotal and dynamic role in the construction of tumor microenvironment (TME), becoming the focus in cancer research and treatment. Multiple cell signaling in ECM remodeling contribute to uncontrolled proliferation, metastasis, immune evasion and drug resistance of cancer. Targeting trilogy of ECM remodeling could be a new strategy during the early-, middle-, advanced-stages of cancer and overcoming drug resistance. Currently nearly 60% of the alternative anticancer drugs are derived from natural products or active ingredients or structural analogs isolated from plants. According to the characteristics of ECM, this manuscript proposes three phases of whole-process management of cancer, including prevention of cancer development in the early stage of cancer (Phase I); prevent the metastasis of tumor in the middle stage of cancer (Phase II); provide a novel method in the use of immunotherapy for advanced cancer (Phase III), and present novel insights on the contribution of natural products use as innovative strategies to exert anticancer effects by targeting components in ECM. Herein, we focus on trilogy of ECM remodeling and the interaction among ECM, cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), and sort out the intervention effects of natural products on the ECM and related targets in the tumor progression, provide a reference for the development of new drugs against tumor metastasis and recurrence.

CXCR7 promotes pulmonary vascular remodeling via targeting p38/MMP2 pathway in pulmonary arterial hypertension

“…A critical component of pulmonary vascular remodeling is ECM remodeling. The ECM primarily consists of collagen, elastin fibers, proteoglycans, and glycoproteins, with collagen and elastin fibers being the predominant structural elements ( 31 ). Generally, MMPs secreted by various cells, especially MMP2, play crucial roles in the development of cardiovascular diseases ( 32 ), and their pertinence to pulmonary vascular reconstruction in both animal models and clinical patients has been reported ( 14 , 33 ).…”

Chlorogenic Acid and Cinnamaldehyde in Combination Inhibit Metastatic Traits and Induce Apoptosis via Akt Downregulation in Breast Cancer Cells

“…The EMT confers an increased migratory capability and aggressiveness to breast carcinoma cells. The survivability of cancer cells is proportional to the ability of the cells to successfully metastasize, which, in turn, is directly linked to the migratory efficiency of the cells [ 57 ]. Therefore, targeting cancer cells’ migratory ability is central to destroying cancer cells’ ability to survive.…”

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy

“…Since matrix stiffness can affect macrophage function and promote tumor progression in the TME, targeting matrix stiffness can promote macrophages toward an antitumor phenotype and may be a new strategy for cancer treatment [ 108 ]. In addition, targeting matrix stiffness can also anchor other stromal cells and delay tumor progression in macrophage-dependent and macrophage-independent ways [ 109 ].…”