EXPERIMENTAL BREAST CANCER LUNG METASTASIS: MORPHOGENESIS AND OPPORTUNITIES FOR BIOCORRECTION.
Keywords:
breast cancer, lung metastasis, metastasis morphogenesis, premetastatic niche, extracellular matrix, fibroblast, macrophage, neutrophil, periostin, fibronectin, matrix metalloproteinase, extracellular vesicle, silymarin, Silybum marianum, biocorrection, histomorphology.Abstract
Breast cancer lung metastasis is not simply the consequence of
disseminated tumor cells entering the pulmonary circulation and forming secondary
nodules. Experimental studies increasingly demonstrate that the lung undergoes
molecular, cellular, stromal, vascular, and extracellular matrix remodeling before and
during metastatic colonization. The present review summarizes experimental evidence
concerning the morphogenesis of breast cancer lung metastases and evaluates the
potential of biocorrection, with particular attention to tissue-protective and anti
inflammatory approaches based on Silybum marianum and its major flavonolignans.
Literature published from 2005 to 2026 was considered, with priority given to
experimental breast cancer models, spontaneous and orthotopic metastasis systems, ex
vivo pulmonary tissue models, immunohistochemistry, single-cell RNA sequencing,
spatial profiling, and extracellular matrix analyses. The reviewed studies demonstrate
that fibronectin, collagen IV, periostin, tenascin-C, matrix metalloproteinases, lysyl
oxidase, inflammatory chemokines, fibroblast subsets, neutrophils, monocytes, and
macrophages participate in the formation of a permissive pulmonary
microenvironment. In 4T1, MMTV-PyMT, SUM159, MDA-MB-231, D2A1 and
related models, changes in pulmonary extracellular matrix and immune-cell
composition were detected before overt metastatic growth. More recent single-cell and
spatial studies identified
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