Background/Aim: Abnormal interaction of epithelial cells with laminin component of basement membrane may account for altered biological behavior of cells, influencing proliferation, adhesion, and motility. In the current study, we investigated the role of 67-kDa laminin receptor (67LR), a high affinity receptor for laminin, in aggressiveness of bile duct carcinoma. Methods: Fifty-two paraffin-embedded specimens and 22 fresh tissues of patients with bile duct carcinoma were analyzed using immunohistologic and real-time polymerase chain reaction techniques, respectively. Expression of 67LR on the bile duct carcinoma QBC939 cells was examined by flow cytometry. The effects of 67LR on the adhesive and invasive abilities of QBC939 cells were determined by adhesion and invasion assay in vitro. Results: Both at the mRNA and protein level, bile duct carcinoma cells expressed a higher level of 67LR than normal epithelial cells (p < 0.01). The expression of 67LR was correlated inversely with differentiation extent of tumor (p < 0.05). The 67LR level was significantly increased in patients with lymph node metastases than in patients without lymph node involvement (p < 0.01). Flow cytometry showed that 69.9 ± 1.1% of QBC939 cells expressed 67LR. Expression of 67LR increased the adhesion and invasion of QBC939 cells. 60 and 120 min of incubation of 67LR antibodies, MLuC5, induced 46.3 ± 2.2 and 61.3 ± 2.1% inhibition of adhesion, respectively. The invasive ability of QBC939 cells to Matrigel was also reduced by 67LR antibodies, MLuC5. Conclusions: Overexpressing 67LR on bile duct carcinoma was associated with invasion and metastasis of bile duct carcinoma. Blockage of 67LR suppressed adhesion and invasion of bile duct carcinoma.
Objectives
This study set out to analyze the difference of heat shock protein 27 (HSP27) and its phosphorylation in patients with lower extremity arteriosclerosis obliterans (LEASO) at different stages. This research also examined their clinical significance in this disease.
Methods
Blood samples from 60 patients with LEASO were collected and divided into two groups according to ankle-brachial index (ABI): group A (ABI ≤ 0.43) and group B (ABI > 0.43). The expression of HSP27 in each stage of Fontaine was measured by ELISA, and the difference of HSP27 concentration and ABI between the two groups was analyzed. Meanwhile, three normal femoral artery specimens (normal group) and three atherosclerotic femoral artery specimens (lesion group) were collected, and HSP27 and its Phospho-HSP27 (Ser15), Phospho-HSP27 (Ser78) and Phospho-HSP27 (Ser82) were detected by western blotting. The data of the protein level between the normal group and the lesion group was made a statistical analysis.
Results
HSP27 concentration in group A was (40.73 ± 15.99) ng/ml, and ABI was 0.26 ± 0.20. HSP27 concentration in group B was (66.30 ± 24.70) ng/ml, and ABI was 0.64 ± 0.20. The protein expression of HSP27 and its phosphorylation in the normal group was 0.82 ± 0.13, 0.66 ± 0.12, 0.91 ± 0.24 and 0.90 ± 0.16, respectively; the protein expression of the lesion group was 0.45 ± 0.08, 0.42 ± 0.09, 0.39 ± 0.12 and 0.58 ± 0.11.
Conclusion
Patients with higher LEASO Fontaine stage and lower ABI had a lower HSP27 concentration. Serum HSP27 concentration was negatively correlated with the severity of LEASO, while HSP27 concentration was positively correlated with ABI value. The content of HSP27 and its phosphorylation of lesion group is significantly lower than that of normal group, which may be closely related to the occurrence and development of atherosclerosis.
The simultaneous inhibition of PLK1 and BRD4 by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and...
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