Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro

Abstract

Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P < 0.001 and P < 0.0001, respectively). Supernatants from activated macrophages increased the adhesion of tumour cells to lymphatic and blood endothelium. Secretion of IL-1β was caspase-1 dependent, and treatment with caspase-1 inhibitor reduced IL-1β production by 73% and concomitantly reduced tumour cell adhesion to levels obtained with resting macrophages. Transmigration of MDA-MB-231 cells across blood and lymphatic endothelial monolayers was significantly increased following IL-1β stimulation. Furthermore, supernatants from activated macrophages increased transmigration of MDA-MB-231 cells across endothelial monolayers, which was abolished by caspase-1 inhibition. IL-1β stimulation of tumour cells significantly increased their migratory ability and a significant increase in migration was observed when MDA-MB-231 cells were stimulated with macrophage conditioned media (two of three donors). Results demonstrate that macrophage production of IL-1β plays an important role in the migration of breast cancer cells and their adhesion to, and transmigration across, blood and lymphatic endothelial cells. Results suggest that IL-1β may play a role in the adhesion to lymphatic endothelial cells in particular.

Interleukin 1 gene polymorphism and susceptibility to disease

“…An in vitro study showed that treatment of endothelial cells with recombinant IL‐1β stimulated the adhesion of breast tumor cells to blood and lymphatic endothelial cells; in addition, it enhanced the transmigration of tumor cells. These data suggest that IL‐1β is likely to be involved in lymphatic vessel invasion by breast cancer …”

“…These data suggest that IL-1β is likely to be involved in lymphatic vessel invasion by breast cancer. 158 Cervical cancer is the second most prevalent malignancy in women. 159 A high susceptibility to cervical cancer in women with of IL1RN VTNR polymorphism was observed in different ethnic groups.…”

Interleukin-1β and Cancer

“…This was sustained by the fact that inhibition or invalidation of NLRP3 in macrophages inhibited the metastatic potential of B16F10 murine melanoma cells in vitro [ 212 ]. Finally, macrophage-derived IL-1β was shown to regulate breast carcinoma cell migration and their adhesion to, and transmigration across, blood and lymphatic endothelial cells [ 213 ]. Cancer cells and fibroblasts can interact with each other to regulate cancer cell migration.…”

Circular RNA in gastric cancer

“…This has led to the discovery of abundant circRNA expression in a variety of eukaryotic organisms. [ 46 ] RT-PCR is the easiest and fastest way to identify circRNA. Primers designed for circRNA reverse splice site sequences allow amplification and quantification of specific circRNAs.…”