The cellular and molecular components involved in pre-metastatic niche formation in colorectal cancer liver metastasis

ABSTRACT

Introduction: Liver metastasis is the main cause of death in colorectal cancer (CRC). Premetastatic niche (PMN), a favorable microenvironment for cancer cells colonization at the distant organ, plays a pivotal role in CRC liver metastasis (CRCLM). Our understanding of the mechanisms mediating the formation of liver PMN in CRC has been significantly advanced in recent years, there are still many challenges and questions that remain.

Areas covered: This review covers cellular and molecular components, and the interaction of theprimary cancer with the resident microenvironment of the distant organ that leads to PMN formation in CRCLM based on the latest literature.

Expert Opinion: Various cellular and molecular events are involved in the liver PMN formation in CRC such as bone marrow-derived cells (BMDCs), hepatic stellate cells, Kupffer cells, extracellular matrix, and CRC-derived factors. The formation of the liver PMN depends on a complex interaction of CRC with the liver microenvironment including BMDCs recruitment, vascularization, immunosuppression, inflammatory response, and extracellular matrix remodeling. This review firstly discusses on the cellular and molecular components contributing to the formation of the liver PMN in CRC, so as to provide new ideas for designing effective therapeutic strategies and prognostic markers for CRCLM.

KEYWORDS:

• Colorectal cancer
• liver metastasis
• pre-metastatic niche
• cellular and molecular components

Article highlights

• Pre-metastatic niche (PMN) formation plays a pivotal role in CRC liver metastasis.

• Various cellular and molecular components are involved in the liver PMN formation, including BMDCs, HSCs, KCs, CAFs, TAMs, CRC-derived chemokines, cytokines, and exosomes.

• The mechanisms of liver PMN formation in CRC are complex and need to be further clarified in the future.

• Understanding the mechanisms of PMN formation can provide new ideas for therapeutic strategies and prognosis predication in CRCLM.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (grant no. 81702922), Natural Science Foundation of Jiangxi, China (grant no. 20181BAB215025), key project of Natural Science Foundation of Jiangxi, China (grant no. 20192ACBL21043), National Health Commission Foundation of Jiangxi, China (grant no. 20191016) and the Natural Science Fund of Education Department of Jiangxi, China (grant no. GJJ170007).