Related Experiment Video
Updated: Aug 7, 2026
The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
Published on: June 16, 2018
Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases
A McGarry Houghton1, Jay L Grisolano, Mary L Baumann
1Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
Matrix metalloproteinases (MMP) have been implicated in virtually all aspects of tumor progression. However, the recent failure of clinical trials employing synthetic MMP inhibitors in cancer chemotherapy has led us to hypothesize that some MMPs may actually serve the host in its defense against tumor progression. Here we show that mice deficient in macrophage elastase (MMP-12) develop significantly more gross Lewis lung carcinoma pulmonary metastases than their wild-type counterparts both in spontaneous and experimental metastasis models. The numbers of micrometastases between the two groups are equivalent; thus, it seems that MMP-12 affects lung tumor growth, and not metastasis formation, per se. MMP-12 is solely macrophage derived in this model, being expressed by tumor-associated macrophages and not by tumor or stromal cells. The presence of MMP-12 is associated with decreased tumor-associated microvessel density in vivo and generates an angiostatic>angiogenic tumor microenvironment that retards lung tumor growth independent of the production of angiostatin. These data define a role for MMP-12 in suppressing the growth of lung metastases and suggest that inhibitors designed to specifically target tumor-promoting MMPs may yet prove effective as cancer therapeutics.
Insights
Macrophage elastase (MMP-12) suppresses lung tumor growth by creating an anti-angiogenic environment. Mice lacking MMP-12 showed increased lung metastases, indicating its protective role in cancer progression.
Area of Science:
- Oncology
- Tumor Microenvironment Biology
- Cancer Metastasis Research
Background:
- Matrix metalloproteinases (MMPs) are broadly implicated in tumor progression.
- Recent clinical trials of synthetic MMP inhibitors have failed in cancer chemotherapy.
- This suggests some MMPs might have a host-protective role against tumors.
Purpose of the Study:
- To investigate the role of macrophage elastase (MMP-12) in lung tumor progression.
- To determine if MMP-12 influences metastasis formation or tumor growth.
- To understand the mechanism by which MMP-12 affects the tumor microenvironment.
Main Methods:
- Utilized genetically modified mice deficient in MMP-12.
- Employed spontaneous and experimental metastasis models of Lewis lung carcinoma.
- Assessed tumor burden, metastasis, and microvessel density in vivo.
- Analyzed the source of MMP-12 expression within the tumor microenvironment.
Main Results:
- Mice deficient in MMP-12 exhibited significantly increased pulmonary metastases compared to wild-type mice.
- MMP-12 deficiency impacted tumor growth rather than initial metastasis formation.
- MMP-12, exclusively expressed by tumor-associated macrophages, correlated with decreased tumor microvessel density.
- MMP-12 promoted an angiostatic tumor microenvironment, hindering tumor growth independently of angiostatin.
Conclusions:
- Macrophage elastase (MMP-12) plays a crucial role in suppressing lung tumor growth.
- MMP-12 acts by modulating the tumor microenvironment towards an anti-angiogenic state.
- Targeting tumor-promoting MMPs, while sparing host-protective ones like MMP-12, may offer effective cancer therapeutic strategies.
