Abstract 3416
Background
Recent studies have shown that the tumor microenvironment plays a significant role in the progression of solid tumors. As an abundant component of the tumor microenvironment, cancer associated fibroblasts (CAFs) have been shown to promote tumorigenesis and cancer aggressiveness, but their molecular characteristics remain poorly understood.
Methods
CAFs and normal fibroblasts (NFs) were isolated from freshly resected specimens from patients with colorectal cancer (CRC). RNA sequence was performed to obtain gene expression profiles of CAFs and NFs. We analyzed the profiles and compared gene expression differences between CAFs and NFs. Moreover, immunohistochemistry, proliferation assay and migration assay were performed for evaluating function of the isolated genes.
Results
RNA sequencing analysis revealed that the gene sets related to the Wnt signaling pathway were highly expressed in CAFs, as well as TGFβ signaling, which is considered to be a regulator of CAFs. Among the components of this pathway, Wnt2 was specifically expressed. Thus, we performed immunohistochemical analysis on Wnt2 in 171 patients who underwent surgery for colorectal adenocarcinoma. Positive staining for Wnt2 was often observed in cancer stroma, although the immunoreactivity was negative or weak in cancer cells. Wnt2 expression in CAFs was significantly correlated with depth of tumor (P < 0.001), lymph node metastasis (P = 0.044), TNM stage (P = 0.010), venous invasion (P < 0.001), liver metastasis (P = 0.045), and recurrence (P = 0.013). Subsequent in vitro analyses revealed that cancer cell invasion and migration were significantly decreased in a conditioned medium from immortalized CAFs transfected with siRNA targeting Wnt2.
Conclusions
The present study showed that Wnt2 expression in CAFs was significantly related to factors leading to tumor progression, such as depth of tumor invasion and lymph node metastasis, as revealed by immunochemical examination. We also demonstrated that Wnt2 protein derived from CAFs induced cancer cell migration and invasion in CRC. These findings suggest that Wnt2 secreted by CAFs is a key role as a critical mediator in CRC progression and is a potential therapeutic target for CRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Japan Society for the Promotion of Science.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2045 - The analysis of treatment sequences and clinical outcomes of thymic carcinoma
Presenter: Arakaki Motoko
Session: Poster Display session 1
Resources:
Abstract
4785 - Transcriptomic Difference of Thymoma and Thymic Carcinoma
Presenter: Naixin Liang
Session: Poster Display session 1
Resources:
Abstract
2864 - A Phase II Trial of Preoperative Chemoradiotherapy and Pembrolizumab for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Presenter: Seoyoung Lee
Session: Poster Display session 1
Resources:
Abstract
5015 - The study of tumor associated exosomes in crosstalk between esophageal carcinoma and lymphatic endothelial cells
Presenter: Weimin Mao
Session: Poster Display session 1
Resources:
Abstract
1339 - Up-regulation of IBSP expression predicts poor prognosis of Esophageal Squamous Cell Carcinoma patients
Presenter: Mingyue Wang
Session: Poster Display session 1
Resources:
Abstract
4083 - PD-L1 expression in primary tumour vs metastatic samples in the Phase 3 MYSTIC study in first-line metastatic (m) NSCLC
Presenter: Niels Reinmuth
Session: Poster Display session 1
Resources:
Abstract
5113 - Assessing the impact of subsequent checkpoint inhibitor (CPI) treatment on overall survival: post hoc analyses from the phase 3 JAVELIN Lung 200 study of avelumab vs docetaxel in platinum-treated locally advanced/metastatic non-small cell lung cancer (NSCLC)
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
4256 - Long-term avelumab treatment in patients with advanced non-small cell lung cancer (NSCLC): post hoc analyses from JAVELIN Solid Tumor
Presenter: Borys Hrinczenko
Session: Poster Display session 1
Resources:
Abstract
4305 - Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: Updated survival and subgroup analysis from the real-world EVIDENS study
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
5128 - IO-Synthesise NSCLC: A pooled analysis of real-world survival outcomes for non-small cell lung cancer patients treated with nivolumab in France and Germany
Presenter: Adrien Dixmier
Session: Poster Display session 1
Resources:
Abstract