Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer

Abstract

BackgroundExtracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease.MethodsECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested.ResultsThe rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes (P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status (P < 0.05) and LMVD (P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining (P < 0.05).ConclusionsBoth ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer.

Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer

“…Therefore, biomarkers that can help to predict prevalence of lymph node metastasis may be helpful for the clinical evaluation. VEGF-C, a subtype of VEGF family, has been reported to participate in the lymphatic metastasis of various solid tumors including ovarian cancers (Bednarek et al 2008;Wu et al 2012;Regan et al 2016;Wang et al 2016). Interestingly, our study revealed that the mRNA expression of VEGF-C was positively correlated with TBL1XR1 levels in clinical tumor tissues.…”

Influence of Cancer-Associated Endometrial Stromal Cells on Hormone-Driven Endometrial Tumor Growth

“…VEGFC has been shown to be associated with promoting aggressive behaviors of tumors including lymphangiogenesis and lymph node metastasis [40, 47, 2, 44]. In addition, hormones can regulate VEGFC expression [40, 47].…”

Profiling of Ileal Carcinoids

“…ECM1 (extracellular matrix protein 1) is a secreted glycoprotein that stimulates angiogenesis and promotes metastasis. ECM1 has been shown to be overexpressed in several different tumor types including breast cancer and hepatocellular carcinoma, and has been found to be associated with metastases and poor prognosis [93,94,95,96]. The importance of tumor stroma for tumor growth and metastasis has been clearly demonstrated in breast cancer.…”