Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma

Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with poor outcome and increasing incidence. We examined by immunohistochemistry the expression of three novel matrix metalloproteinases (MMPs)-MMP-21, MMP-26, and MMP-28-in 44 primary MCC tumors and six lymph node metastases while MMP-10 served as a positive control. Their mRNA expression was also studied in the UISO MCC cell line basally and after various stimulations using quantitative real-time PCR. MMP-28 was observed in tumor cells of 15/44 samples especially in tumors <2 cm in diameter (p = 0.015) while 21/44 specimens showed MMP-28 in the tumor stroma. Expression of MMP-21 was demonstrated in tumor cells of 13/43 samples. MMP-26, instead, was positive in stromal cells (17/44) and its expression associated with tumors >or=2 cm in diameter (p = 0.006). Stromal expression of MMP-10 was the most frequent finding of the studied samples (31/44), but MMP-10 was detected also in tumor cells (17/44). Most of the metastatic lymph nodes expressed MMP-10 and MMP-26. MMP-10, MMP-21, and MMP-28 mRNAs were basally expressed by the UISO cells, and the corresponding proteins were detectable by immunostaining of cultured cells. IFN-alpha and TNF-alpha downregulated MMP-21 and MMP-28 expression. Our results suggest that novel MMPs may have a role in MCC pathogenesis: especially that MMP-26 expression in stroma is associated with larger tumors with poor prognosis. Expression of MMP-21 and MMP-28 seems to associate with the tumors of lesser malignant potential. We also confirm the previous finding on the role of MMP-10 in MCC pathogenesis.

Intricate Functions of Matrix Metalloproteinases in Physiological and Pathological Conditions

“…MMP‐21 may be expressed in various adult tissues, but is normally absent in adult skin (Ahokas et al, ). Pathologically, MMP‐21 is widely documented as an indicator of poor prognosis for a variety of cancer types, including oral squamous cell carcinoma (Pu et al, ), esophageal squamous cell carcinoma (Zhao et al, ), pancreatic adenocarcinoma (Bister et al, ), basal cell carcinoma (Ahokas et al, ), Merkel cell carcinoma (Suomela et al, ), and colorectal cancer (Wu et al, ). The upregulation of MMP‐21 is generally associated with greater spread and metastasis of the tumor, and post‐operative MMP‐21 levels are being investigated for use as an indicator of occult metastasis (Pu et al, ).…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…In several human tumors, including colorectal cancer, breast cancer, prostate cancer, pancreatic cancer, Merkel cell carcinoma, hepatocellular carcinoma, up-regulated levels of MMP-21 have been found, generally in association with poor prognosis (Bister et al, 2007;Hegedüs et al, 2008;Huang et al, 2011;Suomela et al, 2009;Wu et al, 2011b).…”

The function of MMP‑28/TGF‑β induced cell apoptosis in human glioma cells

“…Numerous studies suggest that, under physiological conditions, MMP-28 plays a vital role in embryogenesis and trauma healing ( 7 ). Pathological conditions, such as tumor growth and metastasis, destruction of arthritic cartilage and cardiovascular diseases, are also related to MMPs ( 11 ).…”