Abstract
According to the “seed and soil” theory, metastases are favored by a permissive microenvironment. Proteases of the Adamalysin family (ADAM/ADAMTS) are modifiers of the biological activity of various mediators and could potentially modulate tumor progression and metastases formation.
We aim at determining the involvement of ADAM/ADAMTS at a premetastatic stage in lung parenchyma of mice bearing distant primary tumors.
Balb/c mice were subcutaneously injected in each flank with 2.105 Luc+ 4T1 tumor cells and sacrificed at days 3, 7, 9, 14, 21 and 26 after injection. We determined that tumor-bearing mice are in a premetastatic stage at day 7 and already display pulmonary premetastatic niches characteristics (accumulation of LOX, MMP-9 overexpression and crosslinked collagen IV). At day 7, tumor-bearing mice display a neutrophilic inflammation in lung parenchyma. Boyden assays using the bronchoalveolar lavage fluids showed that modulations of the pulmonary microenvironment in tumor-bearing mice induce recruitment of 4T1 cells. We demonstrated an increased ADAM8 expression at the premetastatic stage in the lungs.
We conclude that distant primary tumors induce an accumulation of neutrophils and an increase of ADAM8 in the lungs before metastases formation. These changes might increase tumor engraftment in the lung.
- Copyright ©ERS 2015