Critical steps to tumor metastasis: alterations of tumor microenvironment and extracellular matrix in the formation of pre-metastatic and metastatic niche

Jianan Zhuyan,Xunxia Bao,Qiubo Wang,Tianhao Zhu,Timing Zhen,Sibo Zhu,Mingyu Chen,Kaichen Xing

doi:10.1186/s13578-020-00453-9

Abstract

For decades, cancer metastasis has been a heated topic for its high mortality. Previous research has shown that pre-metastatic niche and metastatic niche are the 2 crucial steps in cancer metastasis, assisting cancerous cells’ infiltration, survival, and colonization at target sites. More recent studies have unraveled details about the specific mechanisms related to the modification of pro-invasion environments. Here, we will review literatures on extracellular matrix (ECM) alterations, general cancer metastasis, organ specificity, pre-metastatic niche, metastatic niche, colony formation and impact on the course of metastasis. Respectively, the metastatic mechanisms like effect of hypoxia or inflammation on pre-metastatic niche construction, as well as the interaction between cancer cells and local milieu will be discussed. Based on the evidences of metastatic niches, we revisit and discussed the “Seed and Soil” hypothesis by Paget. This review will seek to provide insight into the mechanism of metastatic organ specificity which pre-metastatic niche and metastatic niche might suggest from an evolutionary aspect.

Highlights

Tumors often manifested metastasis during its development: an aggressive and tricky move which caused over 90% of cancer-related deaths [1]
Even though cancer cells metastasize to the same foci, the microenvironment at the target organ still poses a distinctive challenge for a variety of primary cancer types
For pancreatic cancer that metastasize to liver, Kupffer cells in liver could be stimulated by pancreas derived cell through MIF, further induce hepatic stellate cells (HSCs) to deposit fibronectin at extracellular matrix (ECM), eventually summon bone marrow-derived cells (BMDCs) and trigger the pre-metastatic niche (PMN) formation [7]

Summary

Introduction

Tumors often manifested metastasis during its development: an aggressive and tricky move which caused over 90% of cancer-related deaths [1]. For pancreatic cancer that metastasize to liver, Kupffer cells in liver could be stimulated by pancreas derived cell through MIF, further induce hepatic stellate cells (HSCs) to deposit fibronectin at ECM, eventually summon BMDCs and trigger the PMN formation [7]. Periostin, induced change is shown in mouse models of breast cancer, when several factors like TGF-β up-regulated the expression of αSMA and VIM in lung, supporting the successful infiltration of malignant cells through WNT signal pathway [12,13].

Results

Conclusion