SDF-1 promotes metastasis of NSCLC by enhancing chemoattraction of megakaryocytes through the PI3K/Akt signaling pathway.

Lung cancer (LC) is the leading cause of cancer-associated deaths worldwide, among which non-small-cell lung cancer (NSCLC) accounts for 80%. Stromal cell-derived factor-1 (SDF-1) inhibition results in a significant depletion of NSCLC metastasis. Additionally, SDF-1 is the only natural chemokine known to bind and activate the receptor CXCR4. Thus, we attempted to clarify the molecular mechanism of SDF-1 underlying NSCLC progression. Transwell migration, adhesion, and G-LISA assays were used to assess megakaryocytic chemotaxis in vitro and in vivo in terms of megakaryocytic migration, adherence, and RhoA activation, respectively. Western blotting was used to assess PI3K/Akt-associated protein abundances in MEG-01 cells and primary megakaryocytes under the indicated treatment. A hematology analyzer and flow cytometry were used to assess platelet counts in peripheral blood and newly formed platelet counts in Lewis LC mice under different treatments. Immunochemistry and flow cytometry were used to measure CD41+ megakaryocyte numbers in Lewis LC mouse tissue under different treatments. ELISA was used to measure serum TPO levels, and H&E staining was used to detect NSCLC metastasis.SDF-1 receptor knockdown suppressed megakaryocytic chemotaxis in Lewis LC mice. SDF-1 receptor inhibition suppressed megakaryocytic chemotaxis via the PI3K/Akt pathway. SDF-1 receptor knockdown suppressed CD41+ megakaryocyte numbers in vivo through PI3K/Akt signaling. SDF-1 receptor inhibition suppressed CD41+ megakaryocytes to hinder NSCLC metastasis. SDF-1 facilitates NSCLC metastasis by enhancing the chemoattraction of megakaryocytes via the PI3K/Akt signaling pathway, which may provide a potential new direction for seeking therapeutic plans for NSCLC.

[Correlation of cyclooxygenase 2 expression with microlymphatic density and its clinical significance].

OBJECTIVE: To study the expression of cyclooxygenase-2 (COX-2) in esophageal carcinoma and its correlation with microlymphatic density (MLD), and to investigate the clinicopathological and prognostic significance of COX-2 and MLD in patients with esophageal cancer. METHODS: COX-2 expression and MLD were detected by immunohistochemistry in 100 cases of esophageal squamous cell carcinoma. Follow up was available in 76 patients. Multivariable Cox regression was used to analyze the association between the laboratory indices and overall survival of patients with esophageal carcinoma. RESULTS: COX-2 expression was present in 73% of patients. MLD in patients with high COX-2 expression (99.71±39.62) was significantly higher than that in those with low or no COX-2 expression (80.22±30.36) (P<0.05). No correlations were observed between the over expression of COX-2 and clinicopathologic parameters including tumor size and lymphatic metastasis (P<0.05). However, MLD was associated with lymphatic metastasis and the depth of invasion (P<0.05, P<0.01). In the 76 patients with followed up, the median survival was 25.5 months. Cox regression showed that the COX-2 expression, histological grade of the tumor and MLD were risk factors of overall survival of esophageal carcinoma. CONCLUSIONS: COX-2 may contribute to the lymphangiogenesis in the tumor. COX-2 may be a new target point for the treatment of esophageal carcinoma. COX-2 expression and microlymphatic vessel density are of significant prognostic value for esophageal carcinoma.