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
2459 - Does bevacizumab increase joint pain ? Preliminary results of BEVARTHRALGIA Study
Presenter: Vauleon Enora
Session: Poster Display session 1
Resources:
Abstract
4913 - Prostatic cancer androgen deprivation therapy and bone health in carcinoma prostate.
Presenter: Gouri Shankar Bhattacharyya
Session: Poster Display session 1
Resources:
Abstract
1352 - Patterns of care for patients with metastatic bone disease in solid tumors – a cross-sectional study (SAKK 95/16)
Presenter: Michael Mark
Session: Poster Display session 1
Resources:
Abstract
6002 - Infection-Related Mortality in Different Types of Cancers
Presenter: Mohamed Gouda
Session: Poster Display session 1
Resources:
Abstract
5643 - Survival Trends in Critically ill Oncology Patients: impact of patient’s eligibility to post-ICU chemotherapy
Presenter: Edith Borcoman
Session: Poster Display session 1
Resources:
Abstract
3097 - Development and validation of a multivariable prediction model for 6-month mortality in older cancer patients: the GeriAtrIc-Tumor Score of PrEdiction for Early Death (GAIT SPEED)
Presenter: Angeli Angeli
Session: Poster Display session 1
Resources:
Abstract
856 - A Longitudinal Tracking and Quantitative Assessment of Paclitaxel-Induced Peripheral Neurotoxicity
Presenter: Ayumu Matsuoka
Session: Poster Display session 1
Resources:
Abstract
1662 - Efficiency of controlled cryotherapy in prevention of chemotherapy induced peripheral neuropathy (CIPN)
Presenter: Trudi Schaper
Session: Poster Display session 1
Resources:
Abstract
2766 - The Validity of Evaluations for Chemotherapy-Induced Peripheral Neuropathy (CIPN)
Presenter: Teppei Yamada
Session: Poster Display session 1
Resources:
Abstract
5683 - Prevention of chemoradiation-related mucositis in patients with head and neck cancer using dexamethasone-based mouthwash: A phase II randomized double-blind, placebo-controlled study
Presenter: Naiyarat Prasongsook
Session: Poster Display session 1
Resources:
Abstract