The pathological role of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC) progression; special focus on molecular mechanisms and possible therapeutics

Ahmed Hjazi; Faryal Nasir; Rabia Noor; Ali Alsalamy; Rahman S Zabibah; Rosario Mireya Romero-Parra; Muhammad Ikram Ullah; Yasser Fakri Mustafa; Maytham T Qasim; Shaik Vaseem Akram

doi:10.1016/j.prp.2023.154616

The pathological role of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC) progression; special focus on molecular mechanisms and possible therapeutics

Pathol Res Pract. 2023 Aug:248:154616. doi: 10.1016/j.prp.2023.154616. Epub 2023 Jun 13.

Authors

Affiliations

¹ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
² Amna Inayat Medical College, Lahore, Pakistan.
³ College of Medical Technique, Imam Ja'afar Al-Sadiq University, Al-Muthanna 66002, Iraq.
⁴ Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq.
⁵ Universidad Continental, Lima, Perú. Electronic address: rosariomireyar@gmail.com.
⁶ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Aljouf, Saudi Arabia.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq.
⁸ Department of Anesthesia, College of Health and Medical Technololgy, Al-Ayen University, Thi-Qar, Iraq.
⁹ Uttaranchal Institute of Technology, Division of Research & Innovation, Uttaranchal University, Dehradun 248007, India.

PMID: 37379710
DOI: 10.1016/j.prp.2023.154616

Abstract

Colorectal cancer (CRC) is comprised of transformed cells and non-malignant cells including cancer-associated fibroblasts (CAF), endothelial vasculature cells, and tumor-infiltrating cells. These nonmalignant cells, as well as soluble factors (e.g., cytokines), and the extracellular matrix (ECM), form the tumor microenvironment (TME). In general, the cancer cells and their surrounding TME can crosstalk by direct cell-to-cell contact and via soluble factors, such as cytokines (e.g., chemokines). TME not only promotes cancer progression through growth-promoting cytokines but also provides resistance to chemotherapy. Understanding the mechanisms of tumor growth and progression and the roles of chemokines in CRC will likely suggest new therapeutic targets. In this line, a plethora of reports has evidenced the critical role of chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12 or SDF-1) axis in CRC pathogenesis. In the current review, we take a glimpse into the role of the CXCR4/CXCL12 axis in CRC growth, metastasis, angiogenesis, drug resistance, and immune escape. Also, a summary of recent reports concerning targeting CXCR4/CXCL12 axis for CRC management and therapy has been delivered.

Keywords: CXCL12 or SDF-1; CXCR4; Colorectal cancer (CRC); Growth; Metastasis.

Publication types

Review