Functional Role of Matrix gla Protein in Glioma Cell Migration

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor subtype. Despite that metastasis of GBM beyond the central nervous system (CNS) is rare, its malignancy is attributed to the highly infiltration trait, leading to the difficulty of complete surgical excision. Matrix gla protein (MGP) is a vitamin K-dependent small secretory protein, and functions as a calcification inhibitor. The involvement of MGP function in glioma cell dynamics remains to be clarified. The study showed that a low proliferative rat C6 glioma cell line named as C6-2 exhibited faster migratory and invasive capability compared to that observed in a high tumorigenic rat C6 glioma cell line (called as C6-1). Interestingly, C6-2 cells expressed higher levels of MGP molecules than C6-1 cells did. Lentivirus-mediated short hairpin RNA (shRNA) against MGP gene expression (MGP-KD) in C6-2 cells or lentivirus-mediated overexpression of MGP transcripts in C6-1 cells resulted in the morphological alteration of the two cell lines. Moreover, MGP-KD caused a decline in cell migration and invasion ability of C6-2 cells. In contrast, increased expression of MGP in C6-1 cells promoted their cell migration and invasion. The observations were further verified by the results from the implantation of C6-1 and C6-2 cells into ex vivo brain slice and in vivo rat brain. Thus, our results demonstrate that the manipulation of MGP expression in C6 glioma cells can mediate glioma cell migratory activity. Moreover, our findings indicate the possibility that high proliferative glioma cells expressing a high level of MGP may exist and contribute to tumor infiltration and recurrence.

RETRACTED: Silencing of tumor‐suppressive NR_023387 in renal cell carcinoma via promoter hypermethylation and HNF4A deficiency

“…In kidney and liver, ABCC6 deficiency can result in the (Murshed, Schinke, McKee, & Karsenty, 2004;Yao, Zebboudj, Shao, Perez, & Bostrom, 2006). Fu, Wang, Hsieh, Fang, and Tzeng (2018) reported that high proliferative glioma cells can express excessive hydroxyapatite (Khan, Wang, & Khan, 2014), and its expression is also increased in most of the RCC tissues (Levedakou, Strohmeyer, Effert, & Liu, 1992). Furthermore, rescue experiments indicated that ectopic expression of MGP could rescue the pro-proliferative and migration capacities of renal cancer cells after overexpression of NR-023387.…”

The Role of Matrix Gla Protein (MGP) Expression in Paclitaxel and Topotecan Resistant Ovarian Cancer Cell Lines

“…We undertook a comprehensive literature search and did not find any research concerning MGP expression in cancer cells resistant to cytotoxic drugs. However, different levels of MGP transcripts were observed in different human and rat glioblastoma cell lines [ 26 , 43 ] and MGP protein released to culture medium was observed in glioblastoma cell line as well [ 26 ]. These findings confirm that MGP is expressed in different neoplastic cell lines and can be secreted to cell culture medium.…”

SLC39A7 promotes malignant behaviors in glioma via the TNF-α-mediated NF-κB signaling pathway

“…As the most malignant intracranial tumor, the clinical treatment of glioma has encountered great challenges 20 . Current treatment methods have not achieved satisfactory results, and further studies are needed to screen for pathogenic genes and study pathogenic mechanisms to provide new insight into treatment strategies for glioma.…”