Cancer‐associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma

Abstract

Lymph node metastasis is a pathognomonic feature of spreading tumors, and overcoming metastasis is a challenge in attaining more favorable clinical outcomes. Esophageal cancer is an aggressive tumor for which lymph node metastasis is a strong poor prognostic factor, and the tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in particular, has been implicated in esophageal cancer progression. CAFs play a central role in the TME and have been reported to provide suitable conditions for the progression of esophageal cancer, similar to their role in other malignancies. However, little is known concerning the relevance of CAFs to the lymph node metastasis of esophageal cancer. Here, we used clinical samples of esophageal cancer to reveal that CAFs promote lymph node metastasis and subsequently verified the intercellular relationships in vitro and in vivo using an orthotopic metastatic mouse model. In the analysis of clinical samples, FAP + CAFs were strongly associated with lymph node metastasis rather than with other prognostic factors. Furthermore, CAFs affected the ability of esophageal cancer cells to acquire metastatic phenotypes in vitro; this finding was confirmed by data from an in vivo orthotopic metastatic mouse model showing that the number of lymph node metastases increased upon injection of cocultured cancer cells and CAFs. In summary, we verified in vitro and in vivo that the accumulation of CAFs enhances the lymph node metastasis of ESCC. Our data suggest that CAF targeted therapy can reduce lymph node metastasis and improve the prognosis of patients with esophageal cancer in the future.

Exosomal miRNA-139 in cancer-associated fibroblasts inhibits gastric cancer progression by repressing MMP11 expression

“…As one of the important stromal cells in solid tumors, CAFs differentiate into fibroblasts that express α-SMA, playing a central role in promoting tumor growth and progression [17]. Many studies have shown that the accumulation of CAFs in tumor stroma accelerates metastasis [5,[18][19][20]. High expression of α-SMA was found both in GC tumors and CAFs, indicating a pathogenic role of fibroblasts in GC tumor.…”

<p>The Role of β-Arrestin1 in Esophageal Squamous Cell Carcinoma</p>

“…And the tumor invasion and metastasis are still the main causes for the patients' deaths. 1,3,5 In recent years, researches showed a sharp relationship between β-arrestin1 and pathological courses of various tumors. 19,20 This study revealed that the protein level of β-arrestin1 was drastically higher in ESCC tissues than in adjacent tissues.…”

“…Esophageal squamous cell carcinoma (ESCC), the predominant type of esophageal carcinoma, carries a poor prognosis and a low survival rate. [1][2][3][4] Effective tumor markers will play an important role in early diagnosis, treatment monitoring and prognosis evaluation of ESCC.…”

Circular RNAs in the tumour microenvironment

“…CAFs are fibroblasts in a state of continuous activation [120]. As one of the most important components of mesenchyme, CAFs play an important role in tumour growth, proliferation and metastasis [120,121]. In turn, tumour cells can promote fibroblast activation through feedback regulation [122].…”