Metastasis remains the leading cause of cancer-related death. In 1889, Stephen Paget originally proposed the theory "seed-and-soil." Both cancer cell-intrinsic properties ("seed") and fertile microenvironment ("soil") are essential for metastasis formation. To date, accumulating evidences supported the theory using mouse models. The formation of a premetastatic niche has been widely accepted as an accel for metastasis. Similar to tumor microenvironment, various types of cells, such as immune cells, endothelial cells, and fibroblasts are involved in premetastatic niche formation. We have discovered that primary tumors hijack Toll-like receptor 4 (TLR4) signaling to establish a premetastatic niche in the lung by utilizing the endogenous ligands. In this review, we discuss the mechanisms that underlie inflammation-associated premetastatic niche formation upon metastasis, focusing especially on myeloid cells and macrophages as the cells executing and mediating complicated processes.
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http://dx.doi.org/10.1186/s41232-022-00208-8 | DOI Listing |
Cancer Cell
December 2024
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:
Disseminated cancer cells in the peritoneal fluid often colonize omental fat-associated lymphoid clusters but the mechanisms are unclear. Here, we identify that innate-like B cells accumulate in the omentum of mice and women with early-stage ovarian cancer concomitantly with the extrusion of chromatin fibers by neutrophils called neutrophil extracellular traps (NETs). Studies using genetically modified NET-deficient mice, pharmacologic inhibition of NETs, and adoptive B cell transfer show that NETs induce expression of the chemoattractant CXCL13 in the pre-metastatic omentum, stimulating recruitment of peritoneal innate-like B cells that in turn promote expansion of regulatory T cells and omental metastasis through producing interleukin (IL)-10.
View Article and Find Full Text PDFXi Bao Yu Fen Zi Mian Yi Xue Za Zhi
December 2024
The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210000, China. *Corresponding author, E-mail:
Patients with ovarian cancer (OC) are often diagnosed at an advanced stage and have a poor prognosis because of extensive tumour metastasis. Tumour metastasis usually occurs in stages, which means that before the invasion of tumour cells, a pre-metastatic niche (PMN) has been formed to support the subsequent colonisation and growth of tumour cells. Tumour-associated macrophages (TAMs) are highly heterogeneous in terms of origin, phenotype and function.
View Article and Find Full Text PDFNature
January 2025
Laboratory of Cellular Metabolism and Metabolic Regulation, VIB Center for Cancer Biology, VIB, Leuven, Belgium.
Lung metastases occur in up to 54% of patients with metastatic tumours. Contributing factors to this high frequency include the physical properties of the pulmonary system and a less oxidative environment that may favour the survival of cancer cells. Moreover, secreted factors from primary tumours alter immune cells and the extracellular matrix of the lung, creating a permissive pre-metastatic environment primed for the arriving cancer cells.
View Article and Find Full Text PDFCancer Med
January 2025
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Background: Metastasis is the major cause of cancer-related mortality. The premetastatic niche is a promising target for its prevention. However, the generality and cellular dynamics in premetastatic niche formation have remained unclear.
View Article and Find Full Text PDFNat Commun
December 2024
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China.
Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, characterized by an increased proportion of IL-17-expressing γδT (γδ17) and neutrophils.
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