Phosphoglycerate kinase 1‐overexpressing lung cancer cells reduce cyclooxygenase 2 expression and promote anti‐tumor immunity in vivo

Abstract

In addition to the known function in the glycolytic pathway, phosphoglycerate kinase 1 (PGK‐1) promotes reduction of plasmin disulfide bonds leading to angiostatin formation and inhibition of tumor angiogenesis. In this study, the effects of PGK‐1 on anti‐ tumor immunity against lung cancer were evaluated using the Tet‐Off control of PGK‐1 expression in the Lewis lung carcinoma (LLC‐1). There was no significant difference in cell proliferation between parental LLC‐1 and LLC‐1 transduced with PGK‐1 (PGK‐LLC‐1). However, expression of PGK‐1 was found to limit tumor growth in mice subcutaneously injected with the cell lines and tumor growth was restored after doxycycline treatment. In addition, the cell invasion ability of PGK‐LLC‐1 became weaker than that of LLC‐1. Expressions of COX‐2, TGF‐β1 and PGE2 were all found to be down‐regulated in PGK‐LLC‐1. PGK‐LLC‐1 cells treated with doxycycline recovered their COX‐2 protein expression. In the presence of conditioned medium from PGK‐LLC‐1, the endothelial cell migration was reduced. Moreover, PGK‐LLC‐1 also stimulated T lymphocytes to express higher levels of Th1 cytokine (IFN‐γ) and lower levels of IL‐10 in comparison with parental LLC‐1. PGK‐LLC‐1 cells restored the growth rate in immunodeficient mice when compared with the growth rate in normal mice. In the tissue sections, reduced COX‐2 expressions and marked infiltrated CD3 T lymphocytes were observed in the PGK‐LLC‐1 injected group. These findings indicate that overexpression of PGK‐1 in LLC‐1 reduces the COX‐2 expression, and, in turn, affect PGE2, cell invasion, angiogenesis, and the immune functions, and finally inhibit the tumor progression. © 2008 Wiley‐Liss, Inc.

Down-Regulated Phosphoglycerate Kinase 1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Cancer

“…29 Moreover, in lung cancer cells, PGK1 overexpression reduced cyclooxygenase 2 expression, and decreased tumor growth and promoted anti-tumor immunity in vivo. 30,31 PGK1 can bind DNA, influencing DNA replication and repair in mammalian cell nuclei. 32,33 A proteomic analysis of glycolysis in lung cancer tissues revealed that poorly differentiated tumors had significantly lower PGK1 levels compared with moderate or well-differentiated tumors, indicating that PGK1 was down-regulated during lung cancer carcinogenesis.…”

Lung Cancer Proteomics: Recent Advances in Biomarker Discovery

“…Although PGK1 seemed to be a promising prognostic marker, its role in lung cancer is controversial. In fact, in a more recent study, overexpression of PGK1 was found to limit tumor growth in mice subcutaneously injected with the Lewis lung carcinoma cell line (LLC-1), by promoting antitumor immunity [34]. Moreover, LLC-1 cells overexpressing PGK1 showed lower invasion ability and a reduced angiogenesis induction.…”

Effects of Inflammatory Factors on Mesenchymal Stem Cells and Their Role in the Promotion of Tumor Angiogenesis in Colon Cancer

“…Some studies have established that bone marrow-derived MSCs can engraft injured tissues, such as those of the lung, liver, heart, and brain, and recover their function. In the past 10 years, certain institutional studies have confirmed that the use of stem cell transplantation is an important tool in the treatment of several types of malignancies (7)(8)(9). For these reasons (10), such cells are currently being tested for the potential use in cell and gene therapy for tumors (11,12).…”