Matrix metalloproteinase 11 (MMP11) in macrophages promotes the migration of HER2-positive breast cancer cells and monocyte recruitment through CCL2-CCR2 signaling
| Autor: | Hobin Yang, Shin Ung Kang, Young Kee Shin, Chang Ohk Sung, Yoon-La Choi, Mi Jeong Kwon, Soo Youn Cho, Hyojin Jeong, Ha Yeong Chae, Jinil Han |
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| Rok vydání: | 2021 |
| Předmět: |
Chemokine
Stromal cell Receptors CCR2 Breast Neoplasms CCL2 Monocytes Pathology and Forensic Medicine Breast cancer Immune system Matrix Metalloproteinase 11 medicine Humans skin and connective tissue diseases Molecular Biology Chemokine CCL2 biology business.industry Monocyte Macrophages Cancer Endothelial Cells Cell Biology medicine.disease medicine.anatomical_structure Cancer cell biology.protein Cancer research Female business |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology. 102(4) |
| ISSN: | 1530-0307 |
| Popis: | Matrix metalloproteinase 11 (MMP11), a member of the MMP family involved in the degradation of the extracellular matrix, has been implicated in cancer progression. Despite the stromal expression of MMP11 in breast cancer, the prognostic significance and role of MMP11 in immune or stromal cells of breast cancer remain unclear. Based on the immunohistochemical analysis of breast cancer tissues from 497 patients, we demonstrated that MMP11 expression in mononuclear inflammatory cells (predominantly macrophages) is an independent negative prognostic factor in breast cancer, whereas MMP11 expression in tumor cells and fibroblasts is not associated with patient survival. Enforced MMP11 expression in breast cancer cells did not promote cell proliferation and migration. However, MMP11-overexpressing macrophages enhanced the migration of HER2-positive (HER2+) breast cancer cells, recruitment of monocytes, and tube formation of endothelial cells. Furthermore, we found that the chemokine CCL2 secreted from MMP11-overexpressing macrophages activated the MAPK pathway via its receptor CCR2 in breast cancer cells, thereby promoting the migration of HER2+ breast cancer cells through MMP9 upregulation. We also found that MMP11 expression in macrophages was stimulated by MMP11-overepressing HER2+ breast cancer cells. Collectively, our findings provide evidence that MMP11 in macrophages may play a pro-tumoral role in HER2+ breast cancer through interaction with cancer cells, monocytes, and endothelial cells. |
| Databáze: | OpenAIRE |
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