Study of lung structure as a potential pre-metastatic niche in mice with B16 melanoma.

PURPOSE: This study investigated early changes in lung tissue potentially associated with pre-metastatic niche (PMN) development in mice with implanted B16 melanoma by analyzing ultrastructural vascular alterations and markers associated with endothelial activation, vascular-barrier organization, and extracellular matrix (ECM) remodeling.

METHODS

Male C57BL/6 mice were divided into two groups: an intact control group and a group with subcutaneously implanted B16 melanoma. To assess early changes in lung tissue in the absence of morphologically detectable metastases, a set of morphological methods was applied, including light microscopy, transmission electron microscopy with analysis of blood capillary ultrastructure, and immunohistochemical assessment of markers associated with vascular and ECM remodeling.

RESULTS

In the lungs of mice with implanted B16 melanoma, changes in vascular and matrix components potentially associated with PMN development were detected before the appearance of morphologically identifiable metastases, including a decreased thickness of the capillary basement membrane (BM). In parallel, decreased immunoreactivity of Collagen IV, Endoglin, Claudin 1, MCAM (CD146), and MMP2, increased immunoreactivity of VCAM1 and TGF-β, and no significant difference in MMP9 immunoreactivity were observed.

CONCLUSION

The obtained data indicate that, during the early stages of B16 melanoma growth, vascular-matrix alterations can be detected in the lungs of mice and may represent early tumor-associated remodeling events potentially associated with PMN development. These changes include signs of endothelial activation, alterations in vascular-barrier organization, changes in BM thickness, and ECM remodeling.