LAMP‐1 gene is overexpressed in high grade glioma

Abstract

High-grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome-associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP-1 and LAMP-2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP-1 and LAMP-2. The transcriptional activity of LAMP-1 in HGG was significantly higher compared to normal brain and to LAMP-2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP-1 showing again enhanced expression. In conclusion, novel data on LAMP-1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.

Dysregulation of Macropinocytosis Processes in Glioblastomas May Be Exploited to Increase Intracellular Anti-Cancer Drug Levels: The Example of Temozolomide

“…While we did not observe significant changes in LAMP1 expression, Jensen et al [59] found that LAMP1 is more highly expressed in glioblastoma than in diffuse and anaplastic astrocytomas, even though its expression does not correlate with the overall survival of the patient [59,60]. CTBP1/BARS and its downstream target PLD1 , whose activation triggers the closure and the final fission of macropinosomes from the plasma membrane [9,61,62], were found downregulated in high-grade tumors at the mRNA level herein.…”

PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells

“…Whereas it was published that LAMP-1 is constitutively expressed, the specific LAMP-2 expression is known to vary greatly with the cell type 50 . Moreover, the LAMP-1 gene was recently shown to be overexpressed in malignant gliomas 25 . Machado and colleagues also described that lysosomal exocytosis, which is also mainly mediated by LAMP-1, plays a primary role in tumour progression and chemoresistance 51 .…”

“…Notably, the expression of both glycoproteins is linked to each other, which results in a LAMP-1/LAMP-2-homeostasis. Interestingly, LAMP-1 and LAMP-2 expression has been observed in various tumours and has been shown to correlate with a high metastatic potential 23 , 24 , whereas LAMP-1 was also published to be overexpressed in some glioblastomas 25 . In context with cancer, autophagy in general also plays a critical role in the survival of cancerogenic cells undergoing starvation due to deficiencies in nutrition supply within the tumour microenvironment 26 .…”

Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer

“…The overexpression of LAMP1 has been linked to high-grade breast tumors capable of metastasis; hence, its high expression appears to be associated with malignant attributes [ 30 ]. Recent studies have shown LAMP1 overexpression of both mRNA and protein levels in high-grade glioblastoma multiforme (GBM) [ 31 ]. Moreover, high expression levels of LAMP1 in the plasma membrane were observed, inter alia, in colorectal neoplasm tissues, advanced prostate cancer (PCa), and castration-resistant prostate cancer (CRPC) [ 29 , 32 ].…”