Expression and Clinical Significance of Matrix Metalloproteinase-9 in Lymphatic Invasiveness and Metastasis of Breast Cancer

Abstract

BackgroundMatrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear.Methods MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated.ResultsMMP-9+ staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05).ConclusionMMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.

Positive lymph‐node breast cancer patients – activation of NF‐κB in tumor‐associated leukocytes stimulates cytokine secretion that promotes metastasis via C‐C chemokine receptor CCR7

“…These results are consistent with data from another study showing the synergistic effect of IL‐3 or IL‐5 with TNF to induce the secretion of matrix metalloproteinase‐9 by eosinophils . Matrix metalloproteinase‐9 degrades extracellular matrix proteins and facilitates the invasion and lymph node metastasis of breast carcinoma cells .…”

Molecular Mechanisms Underlying Lymphovascular Invasion in Invasive Breast Cancer

“…Stromal cells assist in proteolytic degradation via matrix metalloproteinase (MMP) dictated by the epigenetic regulations from malignant cells. Strong correlations have been reported between LVI and MMP9 [50,51] and MMP1 expression [52]. Overexpression of cancer cell-associated membrane type-1 (MT1)-MMP by BC cells has been reported to induce degradation of the vascular basement membrane and cancer cell intravasation [53].…”

The concentration of matrix metalloproteinase 9 in the tumor and peritumoral tissue as prognostic marker in breast cancer patients

“…We proved that the production of total MMP-9 was higher in peritumoral tissue than in tumor itself with a statistically significant difference. There are only a few papers with studies on the MMP-9 level in peritumoral tissue 12 . We found statistically higher concentrations of MMP-9 in peritumoral than in cancer tissue in the ductal as well as the lobular breast cancer.…”

“…Peritumoral tissue must not be considered as a static organ for energy storage, but as an active factor in the communication between the tumor itself and its microenvironment, producing many cytokines, growth factors and hormones that can affect the tumor growth and development 9 . Matrix metalloproteinases (MMPs) is also known as a gelatinase B and is involved in the degradation of extracellular matrix and type IV collagen, the main component of basement membrane [10][11][12][13] . It promotes cancer progression by increasing the cancer cell proliferation, migration, invasion, metastasis and angiogenesis 14 .…”