The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma

Abstract

Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.

Toad skin extract cinobufatini inhibits migration of human breast carcinoma MDA-MB-231 cells into a model stromal tissue

“…Cancer cell migration and invasion are promoted by a degradation of matrix collagen by metalloproteinases (20)(21)(22). In our previous paper, we reported suppression of MDA-MB-231 cell migration into type I collagen gels in the presence of galardin which is known as an MMP inhibitor (12).…”

PT93, a novel caffeic acid amide derivative, suppresses glioblastoma cells migration, proliferation and MMP-2/−9 expression

“…PT93 was reported as a selective MMP inhibitor, inhibiting MMP-2 and MMP-9 (22). A number of studies demonstrated that MMPs are associated with the ability of tumors to migrate and invade (12,26,27). First generation MMPIs with broad-spectrum MMP inhibitory ability cause unexpected side effects, including musculoskeletal pain and inflammation (12,15,16).…”

The Investigation of ADAMTS16 in Insulin-Induced Human Chondrosarcoma Cells

“…21 Tumor cells, which grow in an uncontrolled manner, have interactions with ECM, immune system cells, and vascular tissue. 22 MMPs and other proteinases (ADAM and ADAMTS) have very important roles in cancer development and progression.…”