Matched-Case Comparison for the Role of Surgery in FIGO Stage Ib1–IIa Squamous Cell Carcinoma of Cervix and Suspicious Para-Aortic Lymph Node Metastasis

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a fatal disease with poor prognosis. The predominant reason for ESCC-related death is distal metastasis. A comprehensive understanding of the molecular mechanism underlying metastasis is needed for improving patient prognosis. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase, which plays a vital role in various physiological and pathophysiological processes. However, the role of TOPK in ESCC metastasis is unclear. Methods Tissue array was used to evaluate the correlation between TOPK expression and ESCC lymph node metastasis. Wound healing assay, transwell assay, and lung metastasis mice model were used to examine the role of TOPK in the migration of ESCC cells in vitro and in vivo. Protein kinase array, mass spectrometry (MS), and molecular modeling were used to examine the pathways and direct target proteins of TOPK that are involved in ESCC metastasis. Additionally, immunofluorescence and western blotting analyses were performed to verify these findings. Results The enhanced expression of TOPK was correlated with lymph node metastasis in the ESCC tissues. TOPK knockdown or treatment with the TOPK inhibitor (HI-TOPK-032) decreased the invasion and migration of ESCC cells in vitro. HI-TOPK-032 also inhibited the lung metastasis in ESCC cell xenograft in vivo model. Moreover, TOPK promoted the invasion of ESCC cells by activating the Src/GSK3β/STAT3 and ERK signaling pathways via γ-catenin. Conclusion The findings of this study reveal that TOPK is involved in ESCC metastasis and promoted the ESCC cell mobility by activating the Src/GSK3β/STAT3 and ERK signaling pathways. This indicated that TOPK may be a potential molecular therapeutic target for ESCC metastasis.

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HIC-5 in cancer-associated fibroblasts contributes to esophageal squamous cell carcinoma progression

Cell Death and Disease ◽

10.1038/s41419-019-2114-z ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 2

Author(s):

Xuanling Du ◽

Qiping Xu ◽

Duyi Pan ◽

Dongke Xu ◽

Baolin Niu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Tumor Stroma ◽

Migration And Invasion ◽

Cancer Associated Fibroblasts ◽

Node Metastasis

AbstractEsophageal squamous cell carcinoma (ESCC) remains one of the most common malignancies in China and has a high metastasis rate and poor prognosis. Cancer-associated fibroblasts (CAFs), a prominent component of the tumor microenvironment, can affect tumor progression and metastasis, but the underlying mechanism remains unclear. There are no studies that explore the role of hydrogen peroxide-inducible clone 5 (HIC-5) in ESCC or compare the role of HIC-5 in CAFs and adjacent noncancerous normal fibroblasts (NFs). In this study, we isolated primary CAFs and NFs from ESCC patients. HIC-5 was highly expressed in CAFs from the tumor stroma of human ESCC patients. HIC-5 knockdown in CAFs inhibited the migration and invasion of ESCC cells in vitro. Supernatant CCL2 levels of CAFs were significantly higher after TGF-β stimulation and lower after knocking down HIC-5 expression, independent of TGF-β treatment. HIC-5 knockdown in CAFs led xenograft tumors derived from ESCC cells mixed with CAFs to present more regular morphology, express higher CDH1, and lower CCL2. Further RNA-seq data showed that HIC-5 has distinct biological functions in CAFs vs. NFs, especially in cell movement and the Rho GTPase signaling kinase pathway, which was verified by wound-healing assays and western blotting. An ESCC tissue microarray revealed that increased HIC-5 expression in the tumor stroma was associated with positive lymph node metastasis and a higher TNM stage. In summary, we identified that stromal HIC-5 was a predictive risk factor for lymph node metastasis in human ESCC and that CAF-derived HIC-5 regulated ESCC cell migration and invasion by regulating cytokines and modifying the ECM.

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Role of right upper mediastinal lymph node metastasis in patients with esophageal squamous cell carcinoma after tri-incisional esophagectomies

Surgery ◽

10.1016/j.surg.2014.05.007 ◽

2014 ◽

Vol 156 (5) ◽

pp. 1269-1277 ◽

Cited By ~ 8

Author(s):

Po-Kuei Hsu ◽

Chien-Sheng Huang ◽

Chih-Cheng Hsieh ◽

Yu-Chung Wu ◽

Wen-Hu Hsu

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Mediastinal Lymph Node ◽

Mediastinal Lymph Node Metastasis ◽

Node Metastasis

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The Correlation Between Tumor-associated Macrophage Infiltration and Progression in Cervical Carcinoma

10.21203/rs.3.rs-115339/v1 ◽

2020 ◽

Author(s):

Fan Guo ◽

Wei na Kong ◽

Gang Zhao ◽

Zhen zhen Cheng ◽

Le Ai ◽

...

Keyword(s):

Cervical Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cervical Carcinoma ◽

Meta Analysis ◽

Critical Role ◽

Experimental Studies ◽

Figo Stage ◽

Node Metastasis

Abstract Background: Tumor microenvironment (TME) plays a particularly important role in the progression, invasion and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of cervical cancer microenvironment. However, the result of studies on the correlation between TAMs and progression in CC is still controversial. This research is aimed at investigating the relationship between TAMs and progression in CC.Method: A total of 100 patients with CC were included in this study. The correlation between TAMs and clinicopathologic features was studied. Also, a systematic literature search was conducted from legitimate electronic databases. This is the first meta-analysis to specifically evaluate the role of different types of TAMs in TME of cervical cancer.Results: In the meta-analysis, high stromal CD68+ TAMs density was relevant to lymph node metastasis (WMD = 11.89, 95% CI 5.30 to 18.47). At the same time, CD163+ M2 TAM density was associated with lymph node metastasis (OR = 2.42, 95% CI 1.09 to 5.37; WMD = 39.37, 95% CI 28.25 to 50.49) and International Federation of Obstetrics and Gynecology (FIGO) stage (WMD = -33.60, 95% CI -45.04 to -22.16). This was confirmed in 100 experimental studies of CC. It supported a critical role of TAMs as a prospective predictor for cervical cancer.Conclusion: Taken together, CD68+ TAM and CD163+ M2 TAM infiltration in cervical cancer was association with tumor progression. And CD163+ M2 TAM infiltration was associated with more advanced FIGO stage and lymph node metastasis in CC.

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