Ultrastructure of gap junction and Cx43 expression in gastric cancer tissues of the patients

Abstract

Introduction: Gap junctions are intercellular channels formed by connexin facilitating communication between cells by allowing transfer of ions and small signaling molecules. Connexin 43 (Cx43) is the most ubiquitous connexin in human tissues. Ample evidence suggests the role of gap junction and its connexins such as connexin 43 in human cancers including gastric cancer, which has an important place in the worldwide incidence of cancer and cancer-related deaths. Due to a number of contradictory studies and insufficient detailed examination in specific cancers, such as gastric cancer, more data on the role of gap junctions and their connexins such as Cx43 involved in gastric cancer remain necessary.

Material and methods: Transmission electron microscopy, Western blotting and RT-PCR were used to show the ultrastructure damage of the gap junction in the gastric carcinoma tissue as well as the expression of Cx43 protein and mRNA, respectively.

Results: Ultrastructure damage of the gap junction in gastric carcinoma tissue was shown while poorly differentiated tissue experienced greater damage. The expression of Cx43 protein and mRNA was higher in healthy gastric tissue than in carcinomatous gastric tissue (p < 0.05). There was higher expression of Cx43 protein and mRNA in high-medium differentiation than in poor differentiation (p < 0.05). Cx43 protein and mRNA expression is not statistically significant for different ages and sex (such as for > 56 and ≤ 56 years) (p > 0.05).

Conclusions: Ultrastructural changes of gap junctions with abnormal Cx43 expression are associated with occurrence and development of gastric cancer, which provides a new research direction for gastric cancer pathogenesis and targeted therapy.

Keywords: Cx43; gap junction; gastric carcinoma; ultrastructure.

Figure 1

Level of Cx43 protein expression in normal and carcinomatous gastric tissues determined by western blot. Error bars indicate standard deviation of the means. Double asterisks indicate t-test p < 0.01. A – Cx43 protein expression in normal and carcinomatous gastric tissues. B – Cx43 protein expression in carcinomatous gastric tissues with different clinicopathological features

Figure 2

Ultrastructure of gap junction in normal gastric tissue, well-moderately differentiated and poorly differentiated gastric carcinoma tissue. The gap junction ultrastructure in the tissues was determined by electron microscopy. A – Complete gap junctions in normal gastric tissue (TEM 100000×, bar = 500 nm). B – Incomplete gap junctions in well-moderately differentiated gastric carcinoma tissue (TEM 100000×, bar = 1 μm). C – Incomplete gap junctions in poorly differentiated gastric carcinoma tissue (TEM100000×, bar = 1 μm)

Figure 3

Lanes of Cx43 protein expressed in gastric cancer and normal gastric mucosa tissues determined by western blot. 1 – normal gastric mucosa, 2 – well and moderately differentiated gastric cancer, 3 – poorly differentiated gastric cancer

Figure 4

Lanes of Cx43 mRNA expressed in gastric cancer and normal gastric mucosa tissues determined by RT-PCR. 1 – Normal gastric mucosa, 2 – well and moderately differentiated gastric cancer, 3 – poorly differentiated gastric cancer

Figure 5

Level of Cx43 mRNA expression in normal and carcinomatous gastric tissues determined by RT-PCR. Error bars indicate standard deviation of the means. Double asterisks indicate t-test p < 0.01. A – Cx43 mRNA expression in normal and carcinomatous gastric tissues. B – Cx43 mRNA expression in carcinomatous gastric tissues with different clinicopathological features