Related Experiment Video
Updated: Jan 28, 2026
Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
Cell Specific Matrix Metalloproteinase-1 Regulates Lung Metastasis Synergistically with Smoke Exposure
A Morishita1, A Gerber2, C-H Gow2
1Kagawa Daigaku, Gastroenterology and Neurology, 1-1 Saiwaicho, Takamatsu, Kagawa, JP 760-8523, Japan.
Abstract:
MMP1, a matrix metalloproteinase that degrades the extracellular matrix, is produced not only by cancer cells but also synthesized in stromal and inflammatory cells during tumorigenesis, invasion and lung metastasis. However, the function of MMP1 expression from host cells, especially tumor-associated macrophages (TAMs), and cells in the lung parenchyma remains to be elucidated. Here we demonstrate that in vitro macrophages co-cultured with tumor cells drastically enhance MMP1 expression, which is further exacerbated upon cigarette smoke exposure. In addition, in vivo, macrophage specific MMP1 was found to have a causative role in primary tumor development and lung metastasis, which was enhanced under smoke exposure as demonstrated in a transgenic mouse model that expressed human MMP1 specifically in macrophages (Mac-MMP1). In contrast, MMP1 from lung cells (Lung-MMP1) reduced colonization to the lung despite the fact that collagen deposition decreased in the Lung-MMP1 mouse tumors. These results demonstrate that the varying cellular source of MMP1 in tumors leads to the complexity observed in the tumor microenvironment. Furthermore, macrophage-specific inhibition of MMP1 secretion may be a potential therapy to aid in the reduction of lung metastasis.
Insights
Matrix metalloproteinase-1 (MMP1) from tumor-associated macrophages promotes tumor growth and lung metastasis, especially with smoking. MMP1 from lung cells has a different effect, highlighting complex tumor microenvironments.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Matrix metalloproteinase-1 (MMP1) degrades extracellular matrix during cancer progression.
- The role of MMP1 from host cells, particularly macrophages and lung cells, in tumorigenesis and metastasis is not fully understood.
Purpose of the Study:
- To investigate the function of MMP1 expressed by tumor-associated macrophages (TAMs) and lung cells in primary tumor development and lung metastasis.
- To determine the impact of cigarette smoke exposure on MMP1 expression and its role in metastasis.
Main Methods:
- Co-culture of macrophages with tumor cells in vitro.
- Exposure to cigarette smoke in vitro and in vivo.
- Generation of transgenic mice expressing human MMP1 specifically in macrophages (Mac-MMP1) or lung cells (Lung-MMP1).
Main Results:
- Macrophage MMP1 expression is enhanced by co-culture with tumor cells and cigarette smoke.
- Macrophage-specific MMP1 (Mac-MMP1) drives primary tumor development and lung metastasis, exacerbated by smoke.
- Lung cell-specific MMP1 (Lung-MMP1) reduced lung colonization, despite decreased collagen deposition in tumors.
Conclusions:
- The cellular origin of MMP1 significantly influences the tumor microenvironment and metastatic potential.
- Macrophage-derived MMP1 plays a critical role in promoting lung metastasis.
- Targeting macrophage MMP1 secretion may represent a therapeutic strategy to reduce lung metastasis.
Related Concept Videos
01:58Cell Specific Gene Expression
01:46Epigenetic Regulation
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:28pH Regulation in Cells
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
01:42The Extracellular Matrix
01:33Hormonal Regulation