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

Dan Liang; Lu Liu; Yunjie Zhao; Zhenyi Luo; Yadi He; Yanping Li; Shiyun Tang; Jianyuan Tang; Nianzhi Chen

doi:10.3389/fphar.2023.1186712

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

Front Pharmacol. 2023 Jul 25:14:1186712. doi: 10.3389/fphar.2023.1186712. eCollection 2023.

Authors

Dan Liang¹, Lu Liu², Yunjie Zhao³, Zhenyi Luo⁴, Yadi He⁵, Yanping Li⁶, Shiyun Tang¹, Jianyuan Tang¹, Nianzhi Chen⁷

Affiliations

¹ Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
³ Key Laboratory of Marine Fishery Resources Exploitment and Utilization of Zhejiang Province, College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.
⁴ Graduate School, Guangxi University of Chinese Medicine, Nanning, China.
⁵ College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁶ School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁷ State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.

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.

Keywords: CAFs, cancer-associated fibroblasts; ECM, extracellular matrix; HA, hyaluronic acid; HSPGs, heparan sulfate proteoglycans; MMPs, matrix metalloproteinases; TAMs, tumor-associated macrophages; TGFβ, transforming growth factor beta; TME, tumor microenvironment.

Publication types

Review

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 82074397, China). The central government guides local science and technology development projects of Sichuan Provincial Science and Technology Department (No. 2021ZYD0107, China). Xinglin Scholar Research Promotion Project of Chengdu University of TCM (grant no. QJRC2022008).