Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype

Abstract

Lymphovascular invasion (LVI) is associated with poor outcome in breast cancer (BC); however, its underlying mechanisms remain ill-defined. LVI in BC develops through complex molecular pathways involving not only the interplay with the surrounding microenvironment along with endothelial cells lining the lymphovascular spaces but also changes in the malignant epithelial cells with the acquisition of more invasive and migration abilities. In this review, we focus on the key features that enable tumour cell detachment from the primary niche, their migration and interaction with the surrounding microenvironment as well as the crosstalk with the vascular endothelial cells, which eventually lead to intravasation of tumour cells and LVI. Intravascular tumour cell survival and migration, their distant site extravasation, stromal invasion and growth are part of the metastatic cascade. Cancer cell migration commences with loss of tumour cells' cohesion initiating the invasion and migration processes which are usually accompanied by the accumulation of specific cellular and molecular changes that enable tumour cells to overcome the blockades of the extracellular matrix, spread into surrounding tissues and interact with stromal cells and immune cells. Thereafter, tumour cells migrate further via interacting with lymphovascular endothelial cells to penetrate the vessel wall leading ultimately to intravasation of cancer cells. Exploring the potential factors influencing cell migration in LVI can help in understanding the underlying mechanisms of LVI to identify targeted therapy in BC.

HOXB7 Overexpression Leads Triple-Negative Breast Cancer Cells to a Less Aggressive Phenotype

“…The cell migration capacity is essential for disease progression and is considered the first step for lymphovascular invasion and tumor metastasis [ 24 ]. The data obtained by the wound-healing assay showed that D3 cells had a significant delay in wound closure capacity, nearly 30%, in all analyzed time points when compared to EV cells ( Figure 3 ; p = 0.027 at 3 h and p < 0.0001 at 6 h, 9 h, 12 h, and 15 h).…”

Potential of AKT2 expression as a predictor of lymph-node metastasis in invasive breast carcinoma of no special type

“…The molecular mechanisms underlying LVI are unclear. In their review, Kariri et al [ 26 ] state that “understanding the role of cancer cell invasion and migration in the differentiation of LVI-related molecular alterations from these driving tumor cell invasion and migration as an early mechanism associated with malignancy is a ‘difficult’ but ‘beatable’ challenge.” However, several hypothetical mechanisms have been proposed. Ribelles et al [ 27 ] suggested that genetic alterations can increase migratory potential.…”

Lymphovascular invasion, race, and the 21-gene recurrence score in early estrogen receptor-positive breast cancer

“…The presence of LVI represents a manifestation of an interaction between the tumor and its microenvironment. The molecular mechanisms underlying LVI are complex and not fully defined, but pathways involving cytokine-receptor interactions have been implicated [26][27][28] . Studies evaluating racial differences in BCA tumor microenvironment have described the differential expression of genes associated with inflammation and angiogenesis 24,25,[29][30][31] , as well as increased microvessel density 29,31 and increased numbers of tumor-associated macrophages 29,32 , which correlate with increased lymphangiogenesis and LVI [33][34][35] , in tumors belonging to Black women.…”